Pathologic characteristics of infectious diseases in macaque monkeys used in biomedical and toxicologic studies

Abstract

Nonhuman primates (NHPs), which have many advantages in scientific research and are often the only relevant animals to use in assessing the safety profiles and biological or pharmacological effects of drug candidates, including biologics. In scientific or developmental experiments, the immune systems of animals can be spontaneously compromised possibly due to background infection, experimental procedure-associated stress, poor physical condition, or intended or unintended mechanisms of action of test articles. Under these circumstances, background, incidental, or opportunistic infections can seriously can significantly complicate the interpretation of research results and findings and consequently affect experimental conclusions. Pathologists and toxicologists must understand the clinical manifestations and pathologic features of infectious diseases and the effects of these diseases on animal physiology and experimental results in addition to the spectrum of infectious diseases in healthy NHP colonies. This review provides an overview of the clinical and pathologic characteristics of common viral, bacterial, fungal, and parasitic infectious diseases in NHPs, especially macaque monkeys, as well as methods for definitive diagnosis of these diseases. Opportunistic infections that can occur in the laboratory setting have also been addressed in this review with examples of cases of infection disease manifestation that was observed or influenced during safety assessment studies or under experimental conditions.

Molecular Detection and Genetic Diversity of Cytomegaloviruses and Lymphocryptoviruses in Free-Roaming and Captive African Green Monkeys (Chlorocebus sabaeus)

“…Since eight of the partial DPOL sequences lacked quality (phred value < 40) and could not be included for homology search for cognate herpesvirus sequences, we could not entirely rule out higher CMV detection rates, or presence of alphaherpesviruses in these AGM samples. All the free-roaming AGMs that tested PCR positive for herpesviruses appeared to be apparently healthy, mirroring previous findings that herpesviruses usually cause asymptomatic infections in immunocompetent NHPs [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 14 , 15 , 50 ].…”

“…In addition, partial sequences of several CMVs and LCVs from various NHPs have been designated as unclassified CMV/LCV viruses within the respective genera [ 1 , 12 , 13 ]. Although CMVs and LCVs have been shown to cause asymptomatic infections in immunocompetent NHPs, they have been associated with clinical conditions in immunosuppressed animals, such as CMV-associated necrotizing enteritis, encephalitis, lymphadenitis and/or pneumonitis and LCV-associated lymphomas and proliferative squamous epithelial lesions (resembling oral hairy leukoplakia in humans) in immunosuppressed macaques [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 14 , 15 ].…”