Natural pathology of the Baboon (Papio spp.).

Over the 20-year period of the study, 4297 baboons were necropsied, and a total of 10,883 diagnoses were made. Table 1 presents the morphologic diagnoses in order by frequency of occurrence, with mean age, numbers of male, female, and unknown sex, and the total number of affected animals per age-group at necropsy. The most common diagnoses in descending order of occurrence were hemorrhage (n = 811, 7.45%), stillborn (n = 636, 5.84%), amyloidosis (n = 559, 5.14%), colitis (n = 558, 5.13%), spondylosis (n = 445, 4.09%), and pneumonia (n = 364, 3.34%). Table 2 presents the number of diagnoses by organ in descending order of occurrence by body system and then organ, with selected references. The systems with the most diagnoses in descending order of occurrence were the digestive (n = 3038, 27.92%), urogenital (n = 2129, 19.56%), musculoskeletal (n = 1330, 12.22%), and respiratory (n = 1235, 11.35%). Table 3 presents the eight most common diagnoses for each of the eight age-groups (perinatal (<1 year), infant (1 to <2 year), juvenile (2 to <6 years), young adult (6 to <11 years), adult (11 to <16 years), older adults (16 to <21 years), elderly (21 to <25 years), and aged (25 years and older). Table 4 summarizes the number of animals in each age-group and the number of each sex by age-group. Figure 1 demonstrates an alternate way to visualize the data. It illustrates the distribution of eight of the more common diagnoses by age at necropsy: colitis, pneumonia, myocarditis, lymphosarcoma, spondylosis, amyloidosis, dermatitis, and nephritis. Although a degenerative disease like amyloidosis is often considered a disease of aged or older animals, occurrence of amyloidosis started as early as 2 years of age. As can be seen by the graphs, pneumonia and colitis are common diagnoses early in life, whereas spondylosis is more common later in life. The frequency of many of the morphologic diagnoses was too low to express a detectable sex difference. Twelve diagnoses showed an association with sex. Males more often were diagnosed with pneumonia, airsacculitis, gingivitis, and glossitis. Females were more likely to be diagnosed with cyst, amyloidosis, steatosis, carcinoma, leiomyoma, adenocarcinoma, nephritis, and dermatitis. Although stillborn and inanition were more frequently diagnosed in males and hemorrhage in females, all three of these diagnoses included many baboons of unknown gender, making any association suspect.

We report 10,883 spontaneous morphologic diagnoses identified in 4297 baboons at necropsy over a 20-year period. The systems with the most diagnoses were the digestive (n = 3038, 27.92%), urogenital (n= 2153, 19.78%), musculoskeletal (n = 1330, 12.22%), and respiratory (n = 1235, 11.35%). The most common overall diagnoses in descending order of occurrence were hemorrhage (n = 811, 7.45%), stillborn (n = 636, 5.84%), amyloidosis (n = 559, 5.14%), colitis (n = 558, 5.13%), spondylosis (n = 445, 4.09%), and pneumonia (n = 364, 3.34%). As would be expected, the most common diagnoses varied with age. The most common diagnoses in baboons dying at <1 year of age were related to perinatal death (stillbirth, in utero death, dystocia, and atelectasis) or poor maternal care (inanition). Cannibalism and hemorrhage were also frequently seen in this age-group and likely also resulted from a difficult birthing process or poor maternal care. Poor maternal care likely continued to account for many of the most common conditions seen in infant (1 to <2 years) baboons such as inanition, dehydration, and hemorrhage; hemorrhage in this group was often secondary to trauma. Inflammatory disease first becomes prominent in this age-group, with pneumonia and colitis appearing as common findings and continuing in all age-groups from infancy (1 to <2 years) to adults (11 to <16 years, pneumonia) and older adults (16 to <21 years, colitis). Infancy (1 to <2 years) was the only age-group with necrosis as one of the most frequent findings. This generally involved the oral cavity, gingiva, and tongue and was suspected to be a sequela of infection by herpesvirus papio 2, which is common in the colony [ 30 , 60 ]. Juvenile baboons (2 to <6 years), like infants, have many diagnoses related to inflammatory disease (pneumonia and colitis) and trauma (hemorrhage). Inanition and emaciation were among the most common findings in these animals. Emaciation and inanition in these baboons could suggest inadequate food intake, but is more likely a result of other disease processes, such as colitis. Colitis was the most frequent diagnosis in this cohort and far exceeded the number of colitis diagnoses in all the other groups. Hyperplasia was also commonly diagnosed in juveniles. The majority of these were lymphoid hyperplasia within the lymph node or spleen and were likely a result of the high number of colitis diagnoses in this age-group. Young adult baboons (6 to <11 years) display a more diverse group of diagnoses. This is the only group where lymphosarcoma and trichobezoar are in the top eight diagnoses. The reason why this age-group appears overrepresented is not known. Dermatitis is also seen with increased frequency in the young adult and adult baboons (6 to <16 years), with a large proportion associated with African histoplasmosis, as previously reported [ 8 ]. Amyloidosis also becomes a common finding in the young adult baboon (6 to <11 years) and is one of the two most common diagnoses in all subsequent age-groups. Amyloidosis has been reported a number of times in baboons, and the relative frequency of naturally occurring amyloidosis suggests the baboon might be a useful animal model for naturally acquired amyloidosis in humans [ 25 ]. Amyloidosis occurs in a range of tissues, including kidney, liver, spleen, lymph nodes, gastrointestinal tract, salivary gland, and endocrine tissues. The largest numbers of cases of amyloidosis were in the islets of Langerhans, with 319 cases. Islet amyloidosis has been reported to be associated with diabetes mellitus in these baboons [ 17 ]. In addition to the diseases of young adults, adult baboons (11 to <16 years) are the first group to have nephritis as a common diagnosis. Nephritis remains one of the top eight diagnoses in all subsequent agegroups. This is also the only age-group where gastritis is frequently seen. Myocarditis is in the top eight diagnoses in adults and also in older adults (16 to <21 years) and may have an association with infection by Trypanosoma cruzi [ 2 ]. Degenerative diseases become more common in older adult baboons (16 to <21 years). Hyperplasia and atrophy of different organs, spondylosis, and cysts in endocrine organs, pancreas, and kidney become common findings. Spondylosis is the second most frequent diagnosis in this group and the most common in all subsequent age-groups. Spondylosis and arthritis are common in elderly (21 to < 25 years) and aged (≥ 25 years) baboons, and baboons could serve as a natural model for these conditions. Endometriosis was the eighth most common diagnosis in aged (≥ 25 years) baboons, and we have previously reported endometriosis in this baboon colony [ 10 ]. Although endometriosis is not in the top eight diagnoses in the older adults (16 to <21 years) and elderly (21 to < 25 years), it was seen in greater numbers in those two groups than in the aged (≥ 25 years) baboons. Few morphologic diagnoses appeared to have a sex association. This was likely in part due to the high number of diagnoses with few affected animals. This necessitated more stringent statistical criteria to identify an association and may have resulted in not identifying some diagnoses. The eight diagnoses with an identified female sex association (cyst, amyloidosis, steatosis, carcinoma, leiomyoma, adenocarcinoma, nephritis, and dermatitis) were predominantly diseases of older baboons. Although other biological factors have not been thoroughly investigated, this finding may be a reflection of the younger average age of males in a breeding colony. Young males are often removed for research studies and so do not appear in this survey of natural lesions. Additionally, fewer adult males are needed in a breeding colony, so once breeding age is reached, females become a sizable majority of the population. The sex association of pneumonia, airsacculitis, gingivitis, and glossitis in males may also reflect this, because younger animals are a more sizable part of the overall male population. Even if the rates of juvenile disease were equal between males and females, the lack of older males would make juvenile diseases appear more frequent when evaluating the overall male population. Neoplasms were found in 395 animals at necropsy, and most have been included in a survey of the baboons at this colony [ 9 ]. The majority of the neoplasms were lymphosarcomas, followed by pituitary adenomas, uterine leiomyomas, cecal adenocarcinomas, and islet cell adenomas. Lymphosarcoma in baboons is often associated with Simian T-cell leukemia virus type 1 (STLV-1) [ 23 ], although an association with STLV was not confirmed in all of the cases in the present study. Pituitary adenomas have also been reported in additional reports from this colony [ 18 ], as have cecal adenocarcinomas [ 48 ], and islet cell adenomas [ 18 ]. Many of the conditions in the current study have been previously described in baboons, including some from our colony (see Table 2 ), but the relative frequency of these findings is rarely described. Previous studies have presented the frequency of diagnoses in baboons, but represented much smaller population groups [ 26 , 31 ]. In one study of captive baboons, the most common diagnoses were pneumonia and enteritis/colitis, often diagnosed together [ 26 ]. Animals with this pneumonia/enteritis complex had typically been in the colony <6 months, so it was suggested that these may be associated with recent shipping and stress [ 11 , 26 ]. In our study, however, pneumonia and colitis were typically seen in younger animals (<5 years-old), which were mostly captive-bred, so the frequency of these diagnoses may be more a function of age than stress associated with shipping. In a previous study, as in the current one, hemorrhage related to trauma was also common, as well as stillbirths and neonatal death [ 26 ]. Some common lesions that were reported in this study that were not in the previous survey [ 26 ] include amyloidosis [ 43 ] and spondylosis, both more associated with older animals [ 56 ], and myocarditis, which we have demonstrated is often associated with positive Trypanosoma serologic titers [ 2 ]. We have presented here the largest survey of morphologic diagnoses in a baboon colony to date. In addition to being a measure of the most common diagnoses that may be expected in a baboon colony, the data presented here also can be used by those interested in utilizing the baboon as a model of particular spontaneous diseases [ 28 ] and can help guide researchers when determining the causes of disease or risk factors for specific pathologic processes [ 50 , 51 ].

During the 20-year period covered in this manuscript (1988–2007), the approximate average baboon population was 5000 animals, 63% female and 37% male, and an average age of 8.3 years (females) and 5.6 years (males). Baboons were housed in two 6-acre metal and concrete corrals, gang cages, and individual metal cages if special handling was required (i.e. for medical care). Animals were fed commercial monkey chow, and water was provided ad libitum . The diets were supplemented with an enrichment fare of grains, fruits, and vegetables. All animal care and procedures were approved by the Southwest Foundation for Biomedical Research Institutional Animal Care and the Use Committee. All baboons that died or were euthanized were necropsied, and tissues were collected for histologic evaluation as required for diagnosis. Tissues were fixed in 10% neutral buffered formalin, processed conventionally, embedded in paraffin, cut at 5 μ m, and stained with hematoxylin and eosin or other stains as needed for diagnosis. When indicated, individual tissues were frozen in liquid nitrogen and stored at −80°F, fixed in 2% glutaraldehyde for electron microscopy, placed in normal saline or transport medium for cytogenetic evaluation, cultured for bacteria and viruses, or frozen in O.C.T. compound for frozen sectioning. Further evaluation using immunohistochemistry was performed as required. The necropsy and histologic evaluation were performed by board-certified veterinary pathologists. Conventional nomenclature was used for all lesions, and results were stored in an internal database (apath). Microscopic findings that were equivocal or otherwise challenging were reviewed by three to five other board-certified veterinary pathologists. If deemed necessary, cases were referred to the Armed Forces Institute of Pathology (AFIP) or other individual pathologists with expertise in the field. A computer search of the pathology database for all gross and microscopic diagnoses relating to baboons was performed. Biopsies and animals on study were excluded. The original medical records, gross necropsy reports, and histopathology reports were retrieved if necessary for the clarification of diagnoses or organs affected. A total of 4297 baboon necropsies were evaluated for this study, these include all baboons that died or were euthanized for natural causes. Stillbirths were considered separate animals with an age of zero; the ages of the dams were not recorded. The cumulative incidence of diagnoses was calculated using the census data for the years 1988 to 2007. The tables were made by using the Statistical Analysis System software (SAS 9.1.3, SAS, Cary, NC, USA). Because of the high number of morphologic diagnoses, evaluation to identify an association with sex was preceded by performing a Bonferroni correction to generate an adjusted alpha. For an adjusted alpha of 0.05, the alpha of the test was determined to be 0.0002154. A function was created in R [ 38 ] that takes as arguments a vector with the number of affected males for each morphologic diagnosis, a vector with the number of affected females for each morphologic diagnosis, the total number of males, and the total number of females. The function iterates through each number for each diagnosis and computes the two-sided Fisher’s exact test for independence. Values ≤0.0002154 were considered significant. Diagnoses that by definition are restricted to one gender (i.e. ovarian cyst, endometriosis, and orchitis) were excluded.