Specific Pathogen-Free Macaques: Definition, History, and Current Production

Abstract

Specific pathogen-free (SPF) macaque colonies are now requested frequently as a resource for research. Such colonies were originally conceived as a means to cull diseased animals from research-dedicated colonies, with the goal of eliminating debilitating or fatal infectious agents from the colony to improve the reproductive capacity of captive research animals. The initial pathogen of concern was Mycobacterium tuberculosis (M.tb.), recognized for many years as a pathogen of nonhuman primates as well as a human health target. More recently attention has focused on four viral pathogens as the basis for an SPF colony: simian type D retrovirus (SRV), simian immunodeficiency virus (SIV), simian T cell lymphotropic/leukemia virus (STLV), and Cercopithecine herpesvirus 1 (CHV-1). New technologies, breeding, and maintenance schemes have emerged to develop and provide SPF primates for research. In this review we focus on the nonhuman primates (NHPs) most common to North American NHP research facilities, Asian macaques, and the most common current research application of these animals, modeling of human AIDS.

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

“…M. tuberculosis can be introduced into a group from a latently infected animal or infected animal handler. Because M. tuberculosis can rapidly spread by the aerosol route and is zoonotic, it is on every list of pathogens used in the definition of specific-pathogen-free macaque colonies (Mansfield, 2005;Lerche and Simmons, 2008;Morton et al, 2008). Since the 1970s, stringent quarantine and testing practices have significantly lowered infection rates in imported animals, primarily due to the guidelines put out by the Centers for Disease Control and Prevention (CDC) and the implementation of surveillance programs in domestic primate centers Roberts and Andrews, 2008).…”

“…However, natural outbreaks of tuberculosis in domestic NHPs, albeit rare, still occur. M. tuberculosis has recently reemerged in macaques imported from Asia and thus remains a constant threat to NHP colonies and animal handlers Morton et al, 2008). The reliability of the intradermal tuberculin skin test, which detects delayed-type hypersensitivity to tuberculin antigens, continues to be debated, but to date it remains the only Institute for Laboratory Animal Research/CDC-approved method for mycobacterium testing of NHPs Roberts and Andrews, 2008).…”

Naturally occurring infections in non-human primates (NHP) and immunotoxicity implications: Discussion sessions

“…Importantly, SPF must be defined/qualified to impart meaning (Morton et al, 2008). The definition should include a list of pathogens that are desired to be absent from the NHP, which implies ongoing testing and surveillance to verify the absence of specific pathogens in a given population.…”

“…TB can be introduced into a group from a latently-infected animal or an infected animal handler. Because M. tuberculosis can rapidly spread by the aerosol route, and is zoonotic, it is on every list of pathogens defining SPF macaque colonies (Mansfield, 2005;Lerche and Simmons, 2008;Morton et al, 2008). Currently, there is no practical way of controlling the definition of SPF, although efforts have been made for some important viruses, as mentioned in the definitions above, based upon safety to human laboratory animal facility workers.…”

Specific Pathogen-Free Status Alters Immunophenotype in Rhesus Macaques: Implications for the Study of Simian Immunodeficiency Virus

“…The National Council on Research Resources (NCRR) and Office of AIDS Research (OAR) of the National Institutes of Health (NIH) have taken a lead role in facilitating and funding the development of SPF macaque colonies primarily in support of HIV/AIDS research. 2,3 Agents targeted for elimination include simian T-lymphotropic virus (STLV), simian immunodeficiency virus (SIV), simian type D retrovirus (SRV), and macacine herpesvirus-1 (BV). In addition to excluding the retroviral agents likely to confound experiments utilizing the SIV macaque model, exclusion of BV has the added benefit of reducing zoonotic risks to human handlers.…”