Fatal Measles Virus Infection in Japanese Macaques (Macaca fuscata)

Abstract

Abstract. An outbreak of natural measles virus infection occurred in a group of Japanese macaques (Macaca fuscata). Over a period of 4 months, 12 of 53 Japanese macaques died following a 2-23-day history of anorexia, diarrhea, and dermatitis. The monkeys were kept in outdoor exhibits but had been moved temporarily into indoor caging and then transferred to new outdoor exhibits. Ten monkeys died while they were in temporary caging, and two monkeys died after they were moved to new outdoor exhibits. The diagnoses were made based on the results of histopathology, immunohistochemistry (IHC), in situ hybridization (ISH), and electron microscopy. Measles virus antigens were detected in the lung, stomach, skin, salivary gland, spleen, and lymph nodes. Tangled, tubular nucleocapsids compatible with paramyxovirus were noted in the lung tissue. As a result of immunosuppression following measles virus infection, various secondary infections including disseminated cytomegalovirus infection, adenoviral and bacterial pneumonia, and Candida albicans-associated gingivitis and esophagitis were noted. The primary infective source or the mode of infection could not be determined in this outbreak, but measles virus may have been transmitted to the monkeys from human visitors while the monkeys were on exhibit.

Overview of known non-human primate pathogens with potential to affect colonies used for toxicity testing

“…Infection in macaques is usually asymptomatic or mild, with fever, conjunctivitis, upper respiratory symptoms, and a maculopapular exanthema frequently observed (Auwaerter et al, 1999;Choi et al, 1999;Willy et al, 1999;El Mubarak et al, 2007). Acute measles infection in humans results in transient immunosuppression secondary to depletion of infected and non-infected B-lymphocytes, CD4…”

“…Similarly, in macaques, marked lymphoid depletion has been observed in lymphoid tissues, including thymus, lymph nodes, and spleen, with immunosuppression persisting for up to 6 months post-infection (McChesney et al, 1989;Wachtman and Mansfield, 2008). Opportunistic infections secondary to measles virus-induced immunosuppression include disseminated cytomegalovirus (CMV, Macacine herpesvirus 3), adenoviral and bacterial pneumonia, and candidiasis (Choi et al, 1999). An important consideration for animal husbandry is that immune dysfunction as a result of measles virus is also known to interfere with the response to Old World mammalian tuberculin (Staley et al, 1995).…”

“…However, a localized form (thrush) causes the formation of white plaques in the oral mucosa and esophagus in some neonates and some stressed or immunocompromised animals. It is a common opportunistic infection secondary to immunosuppressive viruses (e.g., measles virus, SIV, and HIV) and post-transplantation (Baskin et al, 1995;Choi et al, 1999;Leigh et al, 2004). These lesions have abundant pseudohyphae and blastospores, which are identified with GMS or periodic acid Schiff (PAS) stains.…”

“…For example, in experimental simian immunodeficiency virus (SIV) infections, viral, fungal, and parasitic opportunistic pathogens and γ-herpesvirusinduced lymphoid hyperplasia and lymphomas are more common than bacterial pathogens (with the exception of higher-order bacteria such as Mycobacterium spp.). In contrast, simian type D retrovirus (SRV) and measles virus infections impair both humoral and cell-mediated immune responses, and thus, in addition to the list of opportunistic pathogens encountered with SIV-induced immunosuppression, numerous primary and opportunistic bacterial infections are also observed (Osborn et al, 1984;Maul et al, 1986;Choi et al, 1999). T-Lymphocyte-depleting biopharmaceuticals in macaques and humans have been associated with numerous viral and fungal opportunistic infections and with γ-herpesvirus-induced post-transplantation lymphoproliferative disease (van Gorder et al, 1999;Hutto et al, 2003;Norin et al, 2004;Caillard et al, 2005;Haustein et al, 2008;Maki et al, 2008).…”

Impact of Infections and Normal Flora in Nonhuman Primates on Drug Development

“…Symptoms range from fever, rash, and conjunctivitis to mortality, secondary to transient immunosuppression (Choi et al 1999;El Mubarak et al 2007;Willy et al 1999). Once established, measles virus infection spreads rapidly.…”