Chronic Kidney Disease and Kidney Stone in a Wild Chimpanzee (Pan troglodytes verus) in Côte d'Ivoire.

An older wild female chimpanzee (Pan troglodytes) was found dead with a large calcium oxalate stone in the renal pelvis. Histopathological changes included glomerulosclerosis, interstitial nephritis and fibrosis, focal mineralization, and medial hypertrophy. Urinary albumin-creatinine-ratio showed increased values from 15 months before death. Causes of the kidney disease remain unconfirmed.

Granulomatous meningoencephalitis and blindness associated with Mycobacterium tuberculosis complex infection in a senile female chimpanzee (Pan troglodytes).

A 40-year old female chimpanzee (Pan troglodytes) developed hyporexia, weight loss, followed by progressive and complete blindness. Tomography demonstrated an intracranial mass in the rostroventral brain involving the optic chiasm, with a presumptive diagnosis of neoplasm. However, histopathology revealed a granulomatous meningoencephalitis, and tissue samples tested positive for Mycobacterium tuberculosis.

The character of parietal and orbital alterations in the superfamily Hominoidea (families Hominidae [exclusive of Homo] and Hylobotidae).

Parietal external surface disruption routinely referred to as porotic hyperostosis, and orbital alterations (cribra orbitalia), have been attributed to anemia-related bone marrow hyperplasia in humans. A recent study in humans identified that they were actually vascular in nature. Skeletons were examined and epi-illumination surface microscopy was performed on the parietal region and orbit of 156 Hominidae and 123 Hylobotidae to assess if these phenomena were trans-phylogenetic. Trans-cortical channels were recognized on the basis of visualized ectocranial surface defects penetrating the parietal; cribra orbitalia, by alteration of the normally smooth orbital roof appearance. Trans-cortical parietal channels, ranging in size from 20 to 100 µm, are rare in Gorilla and Pan troglodytes and absent in Pan paniscus. They are universally present in adult Pongo abeli and in Hylobatidae, independent of species. Cribra orbitalia was common in Hylobotidae, Pongo pygmaeus and P. abelii, less prevalent in adult P. troglodytes, and not recognized in any Gorilla gorilla or P. paniscus examined. The proliferative form predominated, with the exception of Hylobates concolor and muelleri, in which uncalcified vascular grooves predominated. No correlation was observed between the presence of either trans-cortical channels or cribra orbitalia and fractures, osteoarthritis, or inflammatory arthritis. Parietal alterations observed in apes are trans-cortical channels, analogous to those observed in humans, and do not represent porosity. Similarly, cribra orbitalia in apes is confirmed as vascular in nature. The proliferative form apparently represents calcification of blood vessel walls, indistinguishable from observations in humans. Predominant presence in adults rather than in juveniles suggests that both forms are acquired rather than developmental in derivation. Sex and bone alteration/disease-independence suggests that mechanical, endocrine, and inflammatory phenomena do not contribute to the development of either. Further, independent occurrence of trans-cortical channels and cribra orbitalia suggests that they do not have a shared etiology.

ACUTE NECROTIZING AND EOSINOPHILIC MYOCARDITIS IN A CHIMPANZEE (PAN TROGLODYTES).

Cardiac disease is of importance in captive chimpanzee (Pan troglodytes) health. Here we report an eosinophilic and necrotizing myocarditis in a 17-y-old chimpanzee with no previous history of cardiac disease that progressed to death within 48 h. Toxic and infectious causes were ruled out. The chimpanzee had eosinophilia at different occasions in previous years. The animal had a severe, diffuse, and acute monophasic necrotizing myocarditis, with a moderate lymphoplasmacytic infiltrate that was rich in eosinophils. Ante- and postmortem investigations are compatible with an unusual eosinophilic myocarditis with clinical evolution and morphology comparable with human eosinophilic myocarditis secondary to hypereosinophilic syndrome.

MANAGEMENT OF MEDICAL COMPLICATIONS ASSOCIATED WITH A PRESUMED TETANUS INFECTION IN A NORTHWEST BORNEAN ORANGUTAN (PONGO PYGMAEUS PYGMAEUS).

An 18-yr-old female orangutan (Pongo pygmaeus pygmaeus) developed opisthotonus after sustaining conspecific bite wounds 3 wk earlier. The orangutan developed progressive tetraparesis and dysphagia, despite normal mentation, suggestive of tetanus. A tetanus vaccine had been administered at 2 yr of age, but none since. Brain magnetic resonance imaging, computed tomography, cerebral spinal fluid tap, and bloodwork were unremarkable. Viral, Baylisascaris, and tetanus toxin testing were negative. A femoral central venous catheter (CVC) was placed to provide medications, fluids, and parenteral nutrition. The orangutan received human tetanus immunoglobulin, tetanus toxoid, penicillin, methocarbamol, and analgesia. After 1 wk, the catheterized limb became edematous; a deep vein thrombosis (DVT) was diagnosed ultrasonographically. A cephalic CVC was placed, the limb casted, intravenous therapy reinitiated, and enoxaparin started. The orangutan became mobile days later, and progressively improved. Despite no compliance with enoxaparin, the DVT resolved without residual signs. This is the first reported case of presumptive tetanus and DVT in a great ape.

Brunner's gland hyperplasia in a geriatric chimpanzee (Pan troglodytes), an infrequently reported lesion.

Benign duodenal tumours have very rarely been reported in captive non-human primates and are also rare in human beings. Brunner's gland hyperplasia has not been fully described in a non-human primate. Here, we report Brunner's gland hyperplasia in a geriatric chimpanzee, which was an incidental finding during post-mortem examination.

Idiopathic Myocardial Fibrosis in Captive Chimpanzees (Pan troglodytes).

Cardiovascular disorders and predominantly idiopathic myocardial fibrosis are frequently associated with mortality among zoo-housed chimpanzees (Pan troglodytes). Formalin-fixed whole hearts of deceased chimpanzees housed in zoos (n = 33) and an African sanctuary (n = 2) underwent detailed macroscopic and histopathologic examination using a standardized protocol. Archived histological slides from the hearts of 23 additional African sanctuary-housed chimpanzees were also examined. Myocardial fibrosis (MF) was identified in 30 of 33 (91%) of the zoo-housed chimpanzees but none of the 25 sanctuary-housed chimpanzees. MF was shown to be characterized by both interstitial and replacement fibrosis. Immunophenotyping demonstrated that the fibrotic lesions were accompanied by the increased presence of macrophages, alpha smooth muscle actin-positive myofibroblasts, and a minimal to mild T-cell-dominant leukocyte infiltration. There was no convincing evidence of cardiotropic viral infection or suggestion that diabetes mellitus or vitamin E or selenium deficiency were associated with the presence of the lesion. However, serum vitamin D concentrations among zoo-housed chimpanzees were found to be lower in seasons of low ultraviolet light levels.

DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS IN CAPTIVE GORILLAS (GORILLA SPP.): APPEARANCES AND DIAGNOSIS.

Diffuse idiopathic skeletal hyperostosis (DISH) is a disorder of unknown cause, in which new bone forms in soft tissues attached to the skeleton. Originally described in humans, in whom it is quite common, it is usually asymptomatic. New bone may completely bridge across joints, especially in the spine. However, it can be difficult to distinguish from diseases such as spondyloarthritis and spondylosis. With safer and increased use of radiography in diagnosis, the unfamiliar skeletal changes of asymptomatic DISH may now be coincidentally revealed during investigation of other disorders and result in misdiagnosis and unnecessary treatment. There have been case reports of its occurrence in great apes, but this is the first study to illustrate its appearances in a series of 11 skeletons of western and eastern lowland gorillas (Gorilla gorilla gorilla and Gorilla beringei graueri) from zoos in Europe and the United States. The study combines a review of available clinical and postmortem records with examination of the skeletons and radiologic investigation, such as computed tomography (CT). The results indicate that the disorder is probably common in older (>30 yr) captive gorillas, but that it is asymptomatic. It was not symptomatic during life in any of these animals. Several cases had unexpected features, such as extensive involvement of the thorax and extra-articular sacroiliac and tibiofibular joint fusions that are not typical in humans. By illustrating these skeletons, the study should aid differentiation of DISH from spondylosis (syn spondylosis deformans) and spondyloarhritis. It illustrates those features that are atypical of human DISH. CT scanning is valuable in such cases for examining diagnostically important areas such as sacroiliac joints. Increased awareness of DISH should help with understanding its cause, both in gorillas and humans.

Faster growth corresponds with shallower linear hypoplastic defects in great ape canines.

Deeper or more 'severe' linear enamel hypoplasia (LEH) defects are hypothesized to reflect more severe stress during development, but it is not yet clear how depth is influenced by intrinsic enamel growth patterns. Recent work documented inter- and intraspecific differences in LEH defect depth in extant great apes, with mountain gorillas having shallower defects than other taxa, and females having deeper defects than males. Here, we assess the correspondence of inter- and intraspecific defect depth and intrinsic aspects of enamel growth: enamel extension rates, outer enamel striae of Retzius angles, and linear enamel thickness. Thin sections of great ape canines (n = 40) from Gorilla beringei beringei, Gorilla gorilla gorilla, Pan troglodytes, and Pongo spp. were analyzed. Enamel extension rates were calculated within deciles of enamel-dentine junction length. Linear enamel thickness and the angle of intersection between striae of Retzius and the outer enamel surface were measured in the imbricational enamel. Mountain gorillas have faster enamel extension rates and shallower striae angles than the other taxa examined. Mountain gorillas have thinner imbricational enamel than western lowland gorillas and orangutans, but not chimpanzees. In the combined-taxon sample, females exhibit larger striae angles and thicker imbricational enamel than males. Enamel extension rates are highly negatively correlated with striae angles and LEH defect depth. Enamel growth variation corresponds with documented inter- and intraspecific differences in LEH defect depth in great ape canines. Mountain gorillas have shallower striae angles and faster extension rates than other taxa, which might explain their shallow LEH defect morphology and the underestimation of their LEH prevalence in previous studies. These results suggest that stressors of similar magnitude and timing might produce defects of different depths in one species or sex vs. another, which has implications for interpretations of stress histories in hominins with variable enamel growth patterns.

CONGENITAL HYPOTHYROIDISM IN A BORNEAN ORANGUTAN (PONGO PYGMAEUS) AND A SUMATRAN ORANGUTAN (PONGO ABELII).

Congenital hypothyroidism (CH) in humans is most commonly caused by disruption of thyroid gland development (dysgenesis) or an inherited defect in thyroid hormone biosynthesis (dyshormonogenesis). CH has not been previously documented in great apes. This report describes the clinical presentation, diagnosis, and treatment of CH in a 9-mo-old male Bornean orangutan (Pongo pygmaeus) and a 6-wk-old female Sumatran orangutan (Pongo abelii). Primary CH due to thyroid dysgenesis was confirmed in the Bornean orangutan using sonography and radioisotope scintigraphy. Although commercial thyroid immunoassays are not validated for use in orangutans, in comparison to age-matched controls, thyroid-stimulating hormone level was markedly elevated, and serum thyroxine (T4) and free T4 levels were markedly decreased in both cases. Oral supplementation with levothyroxine sodium resulted in noticeable clinical improvement in both orangutans within 30 days of initiating treatment.

Vernal-like conjunctivitis in a western lowland gorilla (Gorilla gorilla gorilla).

CASE DESCRIPTION: A 17-year-old female western lowland gorilla presented with bilateral ocular discharge, conjunctivitis, and rhinitis that was investigated and treated over a 34-month period. Clinical findings, diagnostic results, treatment, and follow-up are described. CLINICAL FINDING: A mild intermittent mucoid ocular discharge was initially noted. 10 months later, conjunctival hyperemia and thickening developed and progressed rapidly to a mass-like lesion covering the right eye. Hematology revealed eosinophilia. Conjunctival cytology revealed eosinophils and neutrophils, and histopathology revealed a chronic proliferative eosinophilic conjunctivitis. 21 months after, the ocular lesions were investigated the gorilla developed masses within both external nares. Histopathology of the nasal lesions revealed chronic-active eosinophilic rhinitis. TREATMENT AND OUTCOME: Treatment of the gorilla was based on protocols recommended for human patients. Protocols for mild, moderate, and finally severe disease were used, involving topical and oral combinations of treatments. The gorilla eventually responded to systemic immunosuppressant therapy recommended for severe refractory disease. CLINICAL SIGNIFICANCE: To the authors' knowledge, this is the first reported case of vernal-like conjunctivitis in a western lowland gorilla.

ANTEMORTEM DIAGNOSIS AND SUCCESSFUL TREATMENT OF A COMPLETE MOLAR PREGNANCY IN A GERIATRIC BONOBO ( PAN PANISCUS).

A 47-yr-old multiparous female bonobo ( Pan paniscus) tested positive for pregnancy on a routine urine test. Because this geriatric animal was considered postreproductive, oral contraception had been discontinued. Sequential transabdominal ultrasound evaluations were performed under voluntary behavior and revealed that the uterus contained a mass of heterogenous tissue which was rapidly increasing in size. Due to a lack of normal fetal development and the ultrasonographic appearance of the uterine tissue, a molar pregnancy was suspected. Ovariohysterectomy was performed, and a complete hydatidiform mole was confirmed through human chorionic gonadotropin levels as well as gross and histological examination of the uterus. To the authors' knowledge, this is the first time a complete molar pregnancy has been reported antemortem in a nonhuman great ape, although a single case of partial hydatidiform mole was previously documented in a chimpanzee on postmortem examination. This case describes the successful medical and surgical management of complete molar pregnancy in a bonobo and provides support for extending the age range of birth control recommendations in geriatric captive great apes that exhibit active breeding behavior.

Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of ß2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.

Natural pathology of the captive chimpanzee (Pan troglodytes): A 35-year review.

We present the spontaneous pathological lesions identified as a result of necropsy or biopsy for 245 chimpanzees (Pan troglodytes) over a 35-year period. A review of the pathology database was performed for all diagnoses on chimpanzees from 1980 to 2014. All morphologic diagnoses, associated system, organ, etiology, and demographic information were reviewed and analyzed. Cardiomyopathy was the most frequent lesion observed followed by hemosiderosis, hyperplasia, nematodiasis, edema, and hemorrhage. The most frequently affected systems were the gastrointestinal, cardiovascular, urogenital, respiratory, and lymphatic/hematopoietic systems. The most common etiology was undetermined, followed by degenerative, physiologic, neoplastic, parasitic, and bacterial. Perinatal and infant animals were mostly affected by physiologic etiologies and chimpanzee-induced trauma. Bacterial and physiologic etiologies were more common in juvenile animals. Degenerative and physiologic (and neoplastic in geriatric animals) etiologies predominated in adult, middle aged, and geriatric chimpanzees.

COLONIC DIVERTICULOSIS AND DIVERTICULAR HEMORRHAGE IN A GERIATRIC FEMALE ORANGUTAN ( PONGO ABELII).

A 57-yr-old female Sumatran orangutan ( Pongo abelii) presented with signs of intermittent lethargy and inappetence, then subsequently developed profuse hemorrhagic diarrhea. Colonoscopy under anesthesia revealed diverticulosis of the descending colon, with multiple large diverticula containing fecoliths. There was no evidence of diverticulitis, but a regenerative anemia had developed following an acute diverticular bleed. The orangutan recovered with conservative therapy. Colonic diverticulosis has been reported in nonhuman primates and appears to have a similar clinical presentation to the condition as it occurs in humans. This is the first published report of colonic diverticulosis in a great ape.

SUCCESSFUL MANAGEMENT OF CECAL PERFORATION AND FOCAL PERITONITIS IN A GORILLA (GORILLA GORILLA GORILLA).

An 18-yr-old female Western lowland gorilla ( Gorilla gorilla gorilla) presented with acute-onset severe lethargy, bloody vaginal discharge, decreased appetite, and an abnormal posture. The gorilla was diagnosed with a ruptured cecal blind sac with severe adhesions to the right ovary. A typhlectomy and unilateral ovariectomy were performed. Histologic examination identified a severe transmural circumferential typhlitis with rupture and adhesions to the infundibulum and chronic typhlitis. Postoperative management included antibiotics, analgesics, short-term dietary modifications, and probiotics for suspect oral candidiasis. The gorilla made a full clinical recovery and was pregnant within 1 yr of surgery. To the authors' knowledge, this is the first case of successful management of typhlitis in a gorilla. Typhlitis and intestinal rupture should be considered as a differential diagnosis for acute onset severe abdominal pain in gorillas.

MAMMARY GLAND ADENOCARCINOMA IN A MALE BORNEAN ORANGUTAN (PONGO PYGMAEUS).

An adult male Bornean orangutan ( Pongo pygmaeus ) was diagnosed with invasive, poorly differentiated grade 9/9 mammary gland adenocarcinoma from a subcutaneous mass that was surgically removed during a routine preventative health examination. The tumor was tested for estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and HER2 fluorescence in situ hybridization (HER2 FISH). Whole blood was tested for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes. The orangutan was treated orally with two common human breast cancer drugs; tamoxifen and anastrozole. The orangutan lived for 4.5 yr postdetection, dying from an unrelated cause. This is the first reported case of mammary gland adenocarcinoma in a male great ape.

Pauci-immune glomerulonephritis in a captive chimpanzee (Pan troglodytes), and a review of spontaneous cases in animals.

BACKGROUND: Crescentic glomeruli are the hallmark finding in rapidly progressive glomerulonephritis (RPGN) and are characterized by disruption and proliferation of the glomerular capsule and an influx of cells into Bowman's space. Pauci-immune-type RPGN is identified by a lack of immunoglobulins and immune complexes in the glomerular basement membrane. METHODS: Complete necropsy and histology were performed on the affected chimpanzee. Electron microscopy was performed on kidney sections. A search of the literature was performed to identify spontaneous RPGN in animals. RESULTS: We report a case of crescentic glomerulonephritis of the pauci-immune-type in a hepatitis C virus-infected 28-year-old male chimpanzee (Pan troglodytes) who was humanely euthanized for a cardiac-related decline in health. CONCLUSION: To our knowledge, this is the first report describing pauci-immune crescentic glomerulonephritis in a non-human primate.

Comparative Pathology of Aging Great Apes: Bonobos, Chimpanzees, Gorillas, and Orangutans.

The great apes (chimpanzees, bonobos, gorillas, and orangutans) are our closest relatives. Despite the many similarities, there are significant differences in aging among apes, including the human ape. Common to all are dental attrition, periodontitis, tooth loss, osteopenia, and arthritis, although gout is uniquely human and spondyloarthropathy is more prevalent in apes than humans. Humans are more prone to frailty, sarcopenia, osteoporosis, longevity past reproductive senescence, loss of brain volume, and Alzheimer dementia. Cerebral vascular disease occurs in both humans and apes. Cardiovascular disease mortality increases in aging humans and apes, but coronary atherosclerosis is the most significant type in humans. In captive apes, idiopathic myocardial fibrosis and cardiomyopathy predominate, with arteriosclerosis of intramural coronary arteries. Similar cardiac lesions are occasionally seen in wild apes. Vascular changes in heart and kidneys and aortic dissections in gorillas and bonobos suggest that hypertension may be involved in pathogenesis. Chronic kidney disease is common in elderly humans and some aging apes and is linked with cardiovascular disease in orangutans. Neoplasms common to aging humans and apes include uterine leiomyomas in chimpanzees, but other tumors of elderly humans, such as breast, prostate, lung, and colorectal cancers, are uncommon in apes. Among the apes, chimpanzees have been best studied in laboratory settings, and more comparative research is needed into the pathology of geriatric zoo-housed and wild apes. Increasing longevity of humans and apes makes understanding aging processes and diseases imperative for optimizing quality of life in all the ape species.

Spontaneous Reproductive Tract Lesions in Aged Captive Chimpanzees.

Chimpanzees (Pan troglodytes) have served as an important model for studies of reproductive diseases and aging-related disorders in humans. However, limited information is available about spontaneously occurring reproductive tract lesions in aging chimpanzees. In this article, the authors present histopathologic descriptions of lesions identified in the reproductive tract, including the mammary gland, of 33 female and 34 male aged chimpanzees from 3 captive populations. The most common findings in female chimpanzees were ovarian atrophy, uterine leiomyoma, adenomyosis, and endometrial atrophy. The most common findings in male chimpanzees were seminiferous tubule degeneration and lymphocytic infiltrates in the prostate gland. Other less common lesions included an ovarian granulosa cell tumor, cystic endometrial hyperplasia, an endometrial polyp, uterine artery hypertrophy and mineralization, atrophic vaginitis, mammary gland inflammation, prostatic epithelial hyperplasia, dilated seminal vesicles, a sperm granuloma, and lymphocytic infiltrates in the epididymis. The findings in this study closely mimic changes described in the reproductive tract of aged humans, with the exception of a lack of malignant changes observed in the mammary gland and prostate gland.