Abstract

Zoonotic diseases are a concern when working with nonhuman primates (NHPs) in zoological institutions. These concerns for employee health can have implications in the management of these animals. The American Association of Zoo Veterinarian’s (AAZV’s) Infectious Disease Committee formed an ad hoc committee to address current industry safety practices and to provide information on management techniques to minimize the risks of disease transfer to and from NHPs. A set of guidelines was produced which provide a framework of recommendations for managing NHPs in zoological collections. These guidelines aim to reduce human exposure to zoonotic diseases, as well as to reduce human-to-animal disease transmission, while still maintaining a high quality of care and existence for the animals. These guidelines can be used to develop specific institutional policies dealing with NHPs. The information assists staff in assessing and implementing its individual occupational nonhuman primate safety policy.

The guidelines include sections on personnel responsibilities, material required, definitions, various husbandry and veterinary procedures, staff training, policy development and enforcement, public protection, special procedures, and necropsy guidelines. Since this document only addresses safety issues related to disease transmission, it should be part of a more comprehensive occupational health and safety program (OHSP) that includes all hazards: physical, chemical, and biologic. Two recent publications, “Occupational Health and Safety in the Care and Use of Nonhuman Primates” and “Occupational Health and Safety in the Care and Use of Research Animals” published by and available from the National Research Council are valuable resources in developing an OHSP.^1,2

A primary goal of this document is to provide zoo personnel with information they may use to make informed animal and personnel management health risk decisions. Unfortunately, current knowledge does not allow quantitative risk assessments to be performed in many zoological settings. The level of risk associated with each primate taxon and each institution will vary depending on a number of factors including the history of the collection, individual animal medical history, facilities and equipment available for working with the animals, and staff training and expertise. One of the appendices in the guidelines includes a retrovirus information sheet that also covers recommendations for testing and working with positive animals; part of that information is included in this abstract as an example (Appendix 1). Steps being taken to address the current deficit in knowledge include development of medical surveys and recommendations for serologic and other testing to determine presence of disease concerns in captive NHP zoological populations and within individual institutions to aid in assessing risk factors.

After developing the initial set of guidelines, the document has been modified through review by the American Zoo and Aquarium Association’s Animal Health Committee (AZA-AHC), various primate taxon advisory groups, AZA Wildlife Conservation and Management Committee (WCMC), and has been submitted for consideration to the AZA’s Board of Directors. A current version of the guidelines can be viewed at www.aazv.org. It is hoped that this document will assist AZA member institutions as one tool in their programmatic approach to developing and implementing an effective health and safety program.

Appendix 1: Retrovirus Information Sheet

This document is intended to provide both information about, and guidelines for, the care of captive nonhuman primates infected with retroviruses. These viruses may be significant for the health of individual primates and collections as a whole. These viruses present an extremely low, but documented risk of transmission to humans. No human disease has been associated with infection with NHP retroviruses at the time of the writing of these guidelines.

What Are Retroviruses, and What Types Are Found in Nonhuman Primates?

Retroviruses are a large group of RNA viruses that replicate in a unique way, using an enzyme called reverse transcriptase. They are divided into 3 groups: the oncornaviruses, the lentiviruses, and the spumaviruses. Retroviruses are found in all animal species tested to date, and do not always cause disease. The NHP retroviruses that may represent significant zoonotic concerns are listed below:

Oncornaviruses

Simian T-lymphotropic virus (STLV)

• Closely related to human T-cell leukemia virus (HTLV), which is prevalent in many human populations in Asia, Africa and the Americas. HTLV can cause adult T-cell leukemia or lymphoma in a small proportion of infected humans and has also been associated with rare neurologic disorders. There is evidence that HTLV originated from ancient cross-species transmission of STLV.
• There are several distinct but related viruses in this group.
• Seroreactivity has been seen in more than 33 species of Old World primates, both captive and wild. Mode of transmission is thought to be through sexual contact and from dam to infant in breast milk.
• Usually does not cause clinical signs, but has been associated with disease in baboons, African green monkeys, and gorilla.
• A related virus has been found in spider monkeys, and is the only STLV-like virus found in New World primates, but no disease has been associated with it at this time.

Gibbon ape leukemia virus (GaLV)

• Isolated from many captive gibbons (in Asia, USA and Europe) with leukemia.
• Virus is shed in urine and feces, and sexual transmission is also suspected.
• Chronically infected, apparently healthy, antibody negative, virus positive gibbons have been reported.
• The host range for GaLV has not been well explored.

Simian sarcoma virus

• Known from a single isolate from a fibrosarcoma in a woolly monkey which was housed with a gibbon (suspect mutant of GaLV).

Simian retrovirus Type D (SRV)

• Several different serotypes, all unique to macaques.
• Causes acquired immune deficiency and is associated with opportunistic infections and cutaneous and retroperitoneal fibromatosis in captive macaques.
• Transmitted readily through sexual contact, bite wounds and from dam to infant, both pre- and post-natally.
• Apparently healthy carrier animals have been recognized, particularly in cynomolgus macaques. These virus-positive animals may be seronegative, making their identification by serology alone difficult.
• Antibodies to type D retrovirus have been reported in 2 of 247 persons who were occupationally exposed to nonhuman primates. No disease has been identified in these individuals.

Lentiviruses

Simian immunodeficiency virus (SIV)

• Very closely related to human immunodeficiency virus (HIV); in fact, HIV-1 originated from a strain of SIV in chimpanzees. HIV-2 originated from SIV of sooty mangabeys.
• A large percentage of African monkeys, both wild and captive that have been tested, are seropositive for SIV. Each species appears to be infected with its own strain of SIV.
• Clinical signs of immunosuppression due to SIV are rare in African species, but have been recognized in some individuals.
• Asian primates are not natural hosts of SIV and are very susceptible to immunodeficiency disease when they contract SIV.
• Susceptibility of New World primates and prosimians is unknown.
• Natural transmission is thought to be through sexual contact, although bite wounds are also suspected.
• 2 of 3123 (0.06%) samples from humans with occupational exposure to NHPs have tested positive for SIV. These tests, however, represent an unknown number of repeat tests for some of the same individuals, so the prevalence may actually be a bit higher. One of those persons has since reverted to seronegative status. No clinical disease has been noted in either positive person.

Spumaviruses

Simian foamy virus (SFV)

• Complex retroviruses that have been identified with high prevalence in many Old and New World primate species. Foamy viruses have not yet been identified in prosimian species but are suspected to exist.
• A foamy virus genetically closely related to chimpanzee foamy virus has been isolated from a human. No disease association with foamy virus infection in humans has been established.
• No known disease associated with these viruses in their natural NHP hosts.
• 11 of 296 (3.7%) blood samples from humans with occupational exposure to NHPs have tested positive for SFV. At least 4 of these were associated with deep bite wounds. No disease has been noted in any of these individuals.

Nonhuman Primate Testing and Collection Management Recommendations

Although at this time there is little retroviral associated disease in NHPs and no apparent disease from NHP retroviruses in humans, it is recommended that the retroviral status of NHPs collections be determined for reasons of animal health and occupational safety. This can be accomplished by serologic screening of all animals for antibodies to the retroviruses discussed on the retrovirus information sheet (Appendix 1). Animals should be tested at two time points, 1 yr apart. Serologic testing alone is sufficient for detection of SIV and SFV-infected animals. For STLV, a prolonged interval to seroconversion may require repeated testing—over several years, or use of molecular techniques for viral detection at initial screening. For SRV, initial testing by both serology and virus detection methods are required to identify all infected animals. Testing for GaLV is currently not routinely available, but may be available in the near future. Both serology and virus detection methods will need to be employed to detect all infected gibbons.

Once an individual nonhuman primate has been confirmed to be test-positive for any retrovirus, it should be considered infected for life, and retesting for that virus is not necessary. (It should be emphasized that an initial positive test result should be confirmed through follow-up testing before considering the animal “positive.”) Serum banking at the time of annual examination is still recommended, for surveillance of other diseases. If an animal is test-negative, but housed with positive animals, retesting on an annual basis is recommended. If all animals in the collection are negative after repeat testing, and no new animals are introduced, alternate or every third year testing, with serum banking in the off years, is justifiable.

The retroviral status of new acquisitions should be determined prior to introduction. Whenever possible, positive animals should only be introduced into groups with positive animals. Introduction of positive animals into known all-negative groups may result in retrovirus-related disease in the naïve animals. The documented differential pathogenicity of some retroviruses between Asian and African species should reinforce the standard practice of preventing direct contact between members of these two groups of nonhuman primates. The pathogenic potential of variants of these viruses among different species of African primates is largely unknown. There is currently insufficient information to make recommendations for individual risk assessment for movement of NHPs infected with retroviruses. The primate TAG and SSP veterinary advisors should be consulted for specific advice.

Literature Cited

1.  National Research Council of the National Academies. 2003. Occupational Health and Safety in the Care and Use of Nonhuman Primates. The National Academies Press, Washington D.C. (www.nap.edu)

2.  U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, and National Institutes of Health. 1999. Biosafety in Microbiological and Biomedical Laboratories. 4th ed. U.S. Government Printing Office, Washington D.C. (www.cdc.gov/od/ohs/) (VIN editor: link could not be accessed on 2/3/21).