Common and Not-So-Common Pathologic Findings of the Gastrointestinal Tract of Rhesus and Cynomolgus Macaques

Abstract

Rhesus and cynomolgus macaques are the most frequently used nonhuman primate (NHP) species for biomedical research and toxicology studies of novel therapeutics. In recent years, there has been a shortage of laboratory macaques due to a variety of competing factors. This was most recently exacerbated by the surge in NHP research required to address the severe acute respiratory syndrome (SARS)-coronavirus 2 pandemic. Continued support of these important studies has required the use of more varied cohorts of macaques, including animals with different origins, increased exposure to naturally occurring pathogens, and a wider age range. Diarrhea and diseases of the gastrointestinal tract are the most frequently occurring spontaneous findings in macaques of all origins and ages. The purpose of this review is to alert pathologists and scientists involved in NHP research to these findings and their impact on animal health and study endpoints, which may otherwise confound the interpretation of data generated using macaques.

The Influence of Geographical Origin, Age, Sex, and Animal Husbandry on the Spontaneous Histopathology of Laboratory Cynomolgus Macaques (Macaca Fascicularis): A Contemporary Global and Multisite Review of Historical Control Data

“…An in-depth discussion on diarrhea and GIT pathology in macaques is discussed elsewhere in this issue (Johnson et al. 2022) 39 .…”

“…38 Many aspects of these liver lesions (sinusoidal leukocytosis, sinusoidal dilation, Kupffer cell activation, and congestion with hemosiderosis) frequently occur spontaneously in macaques with some opportunistic infections, particularly in the GIT (Figures 3 and 4); and diarrhea and soft feces are generally the most common clinical observation observed in these animals. An in-depth discussion on diarrhea and GIT pathology in macaques is discussed elsewhere in this issue (Johnson et al 2022) 39 .…”

Sarcina sp. as a presumptive cause of fatal acute gastric dilation and gastric emphysema in rhesus macaques

“…3,4,7,9,10,[12][13][14][17][18][19][20][21][22] A definitive etiology and pathogenesis of AGD has yet to be determined; however, a number of predisposing factors are thought to contribute to its development in nonhuman primates, including intragastric fermentation associated with Clostridium perfringens, recent anesthesia, overfeeding, altered feeding schedules, excessive water consumption, and stress. 3,4,7,9,10,[12][13][14]17,[20][21][22] There has been an increase in reports of Sarcina-associated AGD and emphysematous gastritis (EG) in the human and veterinary literature, suggesting that Sarcina-associated AGD and EG is an emerging concern. 2,8,11,19,[23][24][25] Our 2 cases of AGD, one of which also had gastric emphysema, had abundant bacteria morphologically consistent with Sarcina sp.…”

“…2,11,15,16 The bacterium has been reported as an incidental finding in the GI tract of asymptomatic humans and macaques, suggesting that it may be a benign commensal in some cases. 1,5,12,23 To complicate matters, the prevalence of Sarcina is difficult to assess because the bacteria are fastidious and difficult to culture, often requiring techniques such as PCR to confirm their presence. 2,8,19 Identification is typically made when the organisms with distinct morphology are found with light microscopy—the microorganisms are cuboidal, 1.8–3 μm in diameter, and arranged in tetrad packets given their replication in at least 2 planes of growth.…”

Special Issue on the Pathobiology of Laboratory Nonhuman Primates: A Review of Species, Substrain, Geographical Origin, Age, and Modality-Related Factors

“…As such, pathologists are frequently called upon to differentiate spontaneously occurring diarrhea from a test article-related effect. 17 Bringing together a wealth of experience and expertise from the national primate centers, other captive macaque colonies, and commercial toxicologic pathology research centers, this review provides pathologists, toxicologists, and researchers with a comprehensive overview of the main features of GI lesions, which can help determine the etiology, and include or exclude any potential relationship to a test article. Spontaneous findings in the male reproductive system of sexually mature cynomolgus macaques may also present a challenge to pathologists unfamiliar with this age group as there is a paucity of information on this subject.…”