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Authors: Keith Mansfield, D.V.M., Hayley Weston-Murphy, D.V.M.
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OCW Zoological Medicine 2008
Primate Medicine (2009)
K. Mansfield, DVM / H. Murphy, DVM
Cummings School of Veterinary Medicine at Tufts University

1. Learning Objectives and Review

1.1. Learning Objectives

This section on Primate Medicine will give you a good review of the major husbandry challenges, diseases, and clinical approaches to primate health issues. Color coded topics indicate learning objectives that the student should become familiar with. Cases will be presented in class to illustrate these topics. At a minimum, you will be expected to be familiar with the following:

  • Gain an appreciation for the significant zoonotic diseases, especially viral diseases such as Herpes B and bacterial diseases such as tuberculosis.

  • Appreciate that cross species transmission of infectious agents represents a serious threat to captive and wild primates

  • Understanding the main issues involved in keeping primates as pets, especially ethics, husbandry and behavior

  • Be familiar with the preventative health measures recommended for non-human primates in a variety of settings.

  • Be familiar with restraint and anesthesia of non-human primates (including staff training / personal protective gear)

1.2. Anatomy Review

Primates are a diverse group of mammals representing over 600 distinct species and subspecies with worldwide distribution. Taxonomy within the Order is in a constant state of flux as new species are discovered and as new genetic and morphologic data is generated. However such classifications are useful in understanding and describing common features of physiology and disease susceptibility. There is no single common feature that describes the primate order rather the grouping is defined by a collection of common morphologic and behavioral features. An early descriptive definition is still largely correct: Unguiculate, claviculate, placental mammals, with orbits encircled by bone; three kinds of teeth, at least at one time of life; brain always with a posterior lobe and calcarine fissure; the innermost digit of at least one pair of extremities opposable; hallux with a flat nail or none; a well developed caecum; penis pendulous; testes scrotal; always two pectoral mammae (Mivart 1873). See the References and Resources section for suggested anatomy texts. Also refer to the Primate Information Network site for specifics on anatomy and physiology of a variety of species

References and Resources

Conservation Medicine Challenges

Supplemental Readings

1, 2, 3

2. Taxonomy- Order Primates

Taxonomies attempt to group species into broader categories (taxa, sing. taxon) on the basis of substantial similarities and inferred descent from common ancestors. The primate order is divisible into numerous biological taxa on several levels. There are several possible taxonomical systems, and these have changed over time. The following classification is a simplified version

  • Order Primates

    • Suborder Prosimii - Loris, Lemurs, Tarsiers

    • Suborder Anthropoidea

      • Infraorder Platyrrhini - New World Monkeys

      • Infraoder Catarrhini

        • Super family Cercopithecoidea - Old World Monkeys

        • Super family Hominoidea

          • Family Hylobatidae - Gibbons, Simangs

          • Family Pongidae - Orangutans, Gorillas, Chimpanzee, Bonobos

          • Family Hominidae - Humans

Understanding primate taxonomic categories also helps in determining specific husbandry needs and disease susceptibilities. It is also important to understand these categories when discussing zoonotic disease risks. While all non-human primates carry zoonotic diseases, the phylogenetic closeness of the Old World primates makes their zoonoses of particular concern.

In general, the order primates share many behavioral and anatomical features that make them somewhat unique in the animal kingdom. Among these features are their well-developed manual dexterity, their well-developed sense of sight and good hand-eye coordination. They have highly developed cerebral cortices, long infant dependency periods and tend to have very complex social organizations. Physically they are set apart by their prehensile, opposable thumbs, tactile pads and nails on fingers and toes, a precise grip and extremely mobile, strong arms. They have large eyes with binocular vision.

All of these physical and mental adaptations make the husbandry of non-human primates complex and demanding.

gorilla
gorilla

3. Threats to Wild Primate Populations

Critically Endangered PRIMATES from IUCN http://www.redlist.org/

Red-handed howling monkey

Sclater's black lemur

Azuero howling monkey

Golden lemur

Northern brown howling monkey

Alaotran gentle lemur

Azuero spider monkey

Broad-nosed gentle lemur

Brown-headed spider monkey

White-handed gibbon

Woolly spider monkey

Javan gibbon

Northern muriqui

Western Javan gibbon

Brachyteles hypoxanthus

Central Javan gibbon

Northern Bahian blond titi

W. Yunnan black crested gibbon

Coimbra's titi

C. Yunnan black crested gibbon

Trinidad white-fronted capuchin

Black-faced lion tamarin

Margarita Island capuchin

Black lion tamarin

Yellow-breasted capuchin

Golden lion tamarin

White-collared mangabey

Mentawai macaque

Tana River mangabey

Pagai macaque

Roloway guenon

Siberut macaque

Stampf's greater spot-nosed guenon

Yellow-tailed woolly monkey

Bwindi gorilla

Silky sifaka

Mountain gorilla

Diademed sifaka

Cross River gorilla

Perrier's sifaka

Sumatran orang-utang

Golden-crowned sifaka

Miss Waldron's Bay colobus

Propithecus verreauxi ssp. coronatus

Bouvier's red colobus

Tonkin snub-nosed monkey

Tana River red colobus

Squirrel monkey

Red-ruffed lemur

Dealacour's langur

Tonkin hooded black langur

White-headed black langur

White-collared brown lemur

-

  • Habitat destruction

  • Poaching, Hunting for food, Bushmeat trade

  • War/Disaster impacts

  • Natural diseases e.g. Ebola virus

  • Disease threats from human contact (ecotourism, over-population) or introduction of vectors

    • Polio

    • Influenza

    • Measles virus

    • Yellow fever virus

    • Malaria, Filariasis

    • Dracunculiasis

    • Tuberculosis

Pygmy marmoset
Pygmy marmoset

4. Non-Human Primates in Captivity

Since October 10, 1975, US Public Health regulation 42 CFR 71.53 has prohibited the importation of nonhuman primates (NHP) into the United States as pets, and neither nonhuman primates imported since that date nor their offspring may be legally bred or distributed for any uses other than bona fide science, university level education programs, or full time zoological exhibition. The regulation also states that the maintenance of nonhuman primates as pets, hobby, or an avocation with occasional display to others is not a permissible use. All states require that citizens comply with applicable federal regulations but many state officials may be unaware of regulatory restrictions and may be confused by the distinctions among federal agencies regarding restrictions on captively bred animals. Captive bred offspring of animals purported to have been imported before October 10, 1975, are frequently offered for sale. Without proper documentation, it is very difficult to verify the origin of these animals. The American Veterinary Medical Association also has a policy opposing the keeping of wild animals as pets and advising veterinarians to exert their influence to discourage this practice.

Table 1: Federal regulations regarding nonhuman primates

Agency

Statute

Regulations

Subjects

Departments of Health, Centers for Disease Control And Prevention

Public Health Services Act, 42 USCS 201

42 CFR 71.53

Importation, distribution, bona fide uses in US, breeding colony requirements

Department of Agriculture

Animal Welfare Act, 7 USCS 2131-2159

9 CFR Subchapter A

Licenses (breeders, dealers, laboratories, exhibitors, auctions), interstate health certificates, humane care and transport

Department of the Interior, US Fish and Wildlife Service

Endangered Species Act, 16 USCS 1540 Lacey Act, 18 USCS 42

50 CFR 10, 11, 13,14,16

Endangered species, smuggling, interstate sales

To link to the Code of Federal Regulations (CFR) go to http://www.gpoaccess.gov/cfr/about.html and search "primates".

4.1. Primates as Pets

Capuchin
Capuchin

Despite all of the federal regulations and state regulations, there are still plenty of NHP in the pet sector. This is usually one of the worst situations for a non-human primate. Most owners lack the knowledge, devotion, and constant vigilance needed to properly maintain a non-human primate. Major concerns include specialized nutritional requirements, behavioral changes through puberty, proper sanitation and zoonotic disease control. Questions that people should be prepared to answer when considering acquiring a monkey as a pet are:

  1. Are you prepared to live with a wild animal?

  2. Can you deal with the mess?

  3. Is it legal to acquire and keep a monkey in the area where you live?

  4. What will happen when your monkey grows up?

  5. Can you cope with aggression and sharp teeth?

  6. Can you guarantee a good home for the next 20 to 40 years?

  7. Do you have enough space and the right type of space?

  8. Can you afford the cost of feeding and caring for the monkey?

  9. Who will care for your monkey when you are away?

  10. Is there a veterinarian in your area willing to care for the monkey and who has enough experience to provide quality care?

4.2. Husbandry/Nutrition

There are a number of regulations (USDA , AAALAC , OSHA etc.) that pertain to the husbandry, housing, and mental enrichment of NHPs in captivity. Unfortunately, many of these regulations do not extend to privately owned non-human primates. They do serve as excellent standards for minimum quality of care for commercial and research organizations and should be followed by private owners as well.

4.2.1. Nutritional Requirements

Nutritional deficiencies, usually because of owner ignorance, are common problems in pet monkeys. The nutritional requirements of non-human primates are quite complex and vary greatly between the different species. Diets are complex and consist of fruits, vegetables, commercially available monkey chow, and food enrichment items. Primates may be primarily omnivorous, frugivorous, vegetarian, and foragers and their social standing may affect how much and what they eat.

Commercially available dietary products for both New World and Old World primates offer the most balanced nutrition. Vitamin supplementation is required if not using a commercially prepared food. This is critical for New World Primates who rely heavily on exogenous sources of vitamins C and D3. Foraging needs should be met in order to maintain mental enrichment standards.

4.2.2. Vitamin C deficiency (Scurvy)

Scurvy is a common problem in NHP that are not properly supplemented. Although most commercial feeds have adequate levels of vitamin C at the time of packaging, after 90 days of storage, these levels decrease dramatically. Vitamin C deficiency typically presents as scurvy, with clinical signs including swelling of the epiphyses of long bones, hemorrhaging of the gums and periosteum and cephalohematoma. Radiographic changes are helpful in the differential diagnosis of this condition. Maintenance levels of vitamin C are 1-4 mg/kg BW daily and treatment doses are up to 25 mg/kg twice daily for 5 days in severe cases.

Scurvy
Scurvy

4.2.3. Vitamin D3 deficiency.

Both New World (esp. marmosets and tamarins) and Old World primates living in environments without sufficient sunlight require vitamin D3 supplementation. This should be present in commercial monkey diets. Avoid D2 or ergocalciferol since these cannot be utilized. Monkeys deficient in vitamin D3 develop soft bones (metabolic bone disease), long bone deformities, multiple fractures, and increased levels of serum alkaline phosphatase. Treatment consists of 2000 IU/kg vitamin D3 added to the diet. This treatment halts the progression of the process but the major bone deformities are irreversible. UVB or natural sunlight may be helpful in treatment and should be considered for prevention of the problem.

Rickets
Rickets

4.2.4. Hemochromatosis.

Hepatic iron storage disease has been reported in lemurs and marmosets and may impact other neotropical primates. This is likely due to increased availability of dietary iron and the lack of tannins in the diet which are found in their natural environment (similar to the etiology suspected for toucans). Lemurs should be fed a special lemur commercial diet. Citrus fruits and/or added ascorbic acid should be avoided since this will increase the availability of iron. Hepatic neoplasia may be a consequence of hemochromoatosis. (This is still controversial).

5. Health and Disease with a Special Emphasis on Zoonoses

Baby macaque
Baby macaque

Because of the evolutionary closeness between non-human primates and human primates, they share a lot of the same disease concerns. Zoonotic risks are higher to humans when dealing with non-human primates, and diseases that are transferred from natural host reservoirs to non-natural hosts can often become devastating clinical syndromes. It is beyond the scope of this report to cover, in depth, all of the zoonotic diseases transmissible from nonhuman primate (NHP) to humans. It would be negligent not to state that the keeping of NHP as pets should be strongly discouraged, both from an animal health and welfare point of view, as well as a human health concern. It should also be pointed out that seeing NHPs in a private veterinary clinical setting should be approached with caution. Only a well-equipped practice, with staff that have been properly trained in primate handling and have been informed about and screened for zoonotic disease, should take on this challenge. Even then, the occupational health and safety hazards, ethical and legal ramifications can be enormous.

5.1. Viral Zoonoses

This group of zoonotic diseases is probably the most dangerous. They can be both diagnostically challenging, as well as devastating, when passed from the NHP to humans.

5.1.1. Herpes Viruses (Herpesviridae)

This viral family is one of the more common groups of viruses found in NHPs, as well as one of the best publicized. Herpes infections are responsible for a wide range of symptoms ranging from inapparent infections to fatal disease.

Herpesviridae

subfamily

genus

virus

Natural host

Non-natural host

alphaherpesvirinae

Simplexvirus

Herpes simplex virus 1 (HSV1)

man

Tamarins, marmosets, owl monkeys

B virus

macaques

Humans; other primate species

Herpesvirus tamrinus 1(HVT1)

Squirrel monkeys

Tamarins, marmosets, owl monkeys

varicellovirus

Simian varicella

macaques

African primates; macaques?

betaherpesvirinae

Cytomegalovirus

CMVs

All NHPs

Not described

Roseolovirus

HHV-6

man

Not described

Gammaherpesvirinae

Lymphocryptoviruses

EBV

man

Tamarins, marmosets, owl monkeys

Primate LCVs

All NHPs

Not described

Rhadinoviruses

Herpesvirus saimiri

Squirrel monkey

Tamarins, marmosets, owl monkeys

HHV-8

man

Not described

RRV

macaques

Not described

RFHV

macaques

Not described

5.1.1.1. Herpes B

Probably the most famous of the herpes viruses is Herpes B (Macacine herpesvirus 1 or herpesvirus simiae), which is a disease of all macaque species, including rhesus, cynomolgus, bonnet, Japanese, Taiwan, stump tail, and pigtail macaques. No other Old World or New World monkeys are known to naturally harbor B-viruses. B-virus may be fatal in several non-macaque species of monkeys including patas, black and white colobus, capuchin, Debrazza monkeys and common marmosets.

Only a small percentage of infected macaques will present with clinical signs of ulcers and white plagues on lips, nares, tongue, genitalia, and palate and they may have conjunctivitis. Most however are asymptomatic. Like herpes simplex virus infections in humans, B-virus infections in monkeys can be characterized by life long infections with periodic activation and viral shedding in saliva and genital secretions. The primary mode of transmission between monkeys is by sexual activity and bites, while transmission to humans may be through bites, scratches, or contact with infected blood or urinary secretions to mucus membranes.

Although symptomatic human infections from exposure to herpes B virus are rare, when symptomatic infection does occur, the infection is severe and often fatal (79%). Between 1933 and 1994, fewer than 40 cases of herpes B in humans had been documented by the CDC and of the 24 known symptomatic cases reviewed by 1992, 79% were fatal. The incubation period in man is anywhere from 2 weeks to 6 months and clinical signs starting out as pain, numbness, vesicles, and neuresthesia or paresthesia at site of exposure. In the exposed extremity there may be a regional lymphadenopathy, fever, muscle weakness or paralysis and conjunctivitis, often accompanied by generalized malaise and flu-like symptoms. The disease then may progress to cause persistent hiccups, sinusitis, neck stiffness, headache, flu-like symptoms, nausea, vomiting, confusion, brain stem damage and fatal meningoencephalitis in humans. Most surviving humans have moderate to severe neurological impairment. Antiviral treatments given early in the course of the disease may prevent progression of the disease and has proven to be life saving in some patients. These antiviral medications must be taken continuously throughout life to prevent recrudescence of disease. Rapid diagnosis and treatment is essential in preventing permanent disability and death in patients that are symptomatic.

Herpes B
Herpes B

Diagnostic testing for the detection of Herpes B can be done by serology to detect antibodies. This does not detect animals that may be shedding the virus; this can be done by obtaining swabs from the conjunctiva, oral cavity, and/or genitalia for viral culture. If B-virus is cultured from any of these sites, that is confirmation that an animal is actively shedding virus. A negative antibody test or viral culture result, however, does not exclude the possibility of B-virus infection or viral shedding.

It is safest to assume that all macaques are carrying and capable of transmitting Herpes B infection. All facilities that house animal potentially infected with B virus should have a comprehensive B virus prevention and control program in place. Elements of such a program should include: 1) standard operating procedures for handling macaques and their tissues; 2) education and training of all personnel having potential contact with macaques; 3) the presence of supplies for immediate patient first aid; 4) maintenance of nonhuman primate related injury database; 5) the required use of appropriate personal protective equipment; 6) access to medical care staff with expertise in Herpes B virus risk assessment, diagnosis, treatment and follow up; 7) periodic review of existing procedures and policies to ensure employee safety and compliance.

What to do if you are injured

Stop

Rapid response is essential; experimental work indicates that B virus enters cells within 5 minutes of exposure; understand that individuals often rationalize to decrease the significance of a potential exposure

Wash/cleanse area

Immediately scrub the wound with running water and detergent for 15 minutes; or flush mucous membrane for 15 minutes with running water or saline.

Report

Contact medical care staff so that appropriate risk assessment and follow p may be provided

Herpes B
Herpes B

5.1.1.2. Other Pathogenic Herpes Viruses

Other herpes viruses that can be of concern, either because of zoonotic risks or transmission between susceptible species of monkeys are:

Alphaherpesvirinae

  • Human herpesvirus 1 (Herpesvirus simplex): Both HSV1 and HSV2 have been known to be transmissible from man to monkeys (experimentally). In owl monkeys, tree shrews, gibbons, marmosets and cebus monkeys, HSV1 causes high morbidity and mortality following transmission from human handlers. Infection results in a disseminated disease causing encephalitis, stomatitis and severe hepatitis.

  • Herpesvirus tamarinus: viral herpes in tamarins and marmosets that may cause severe clinical disease, including hepatitis, in those species. Can be devastating in owl monkeys and tamarins resulting in a rapidly fatal disseminated viral infection

Herpes conjunctivitis
Herpes conjunctivitis

HSV1
HSV1

  • Simian Varicella viruses (SVV): This is a group of seven simian herpesviruses that closely resemble varicella-zoster in man. They include Liverpool vervet monkey virus, Patas monkey herpesvirus, Delta herpesvirus, Medical Lake macaque virus, Herpesvirus cyclopis, Chimpanzee herpesvirus, and Gorilla herpesvirus. Infection with any of the seven viruses, in general, causes high morbidity and mortality and varies greatly depending on the virus and species involved. Animals may be latently infected and develop disease following reactivation. Clinical signs can range from severe dermatitis to a severe, life threatening and often-fatal exanthematous disease.

Simian Varicella
Simian Varicella

Betaherpesvirinae

  • Simian Cytomegaloviruses (CMV): Cytomegaloviruses are relatively host specific and in its natural hosts tend to cause latent infections with relatively no clinical signs. Most NHPs are infected with species specific CMVs. Reactivation with disseminated disease may occur following immunosuppression.

Gammaherpesvirinae

  • Lymphocryptoviruses. Nearly all NHPs are infected with species specific lymphocrytpoviruses related to human EBV. Following infection lifelong latency is established. Rarely infection may be associated with malignant lymphoma or lymphoproliferative disorders.

  • Rhadinoviruses. Many old world primates and some new world primates are infected with rhadinoviruses. Herpes virus saimiri is found in nearly all squirrel monkeys that is carried asymptomatically and without clinical effect. When this virus is inadvertently transmitted to marmosets, tamarins or owl monkeys, there is rapid induction of malignant lymphoma within 21 -28 days. A related virus has been identified in spider monkeys.

Herpes lesion
Herpes lesion

Due to the risk of cross species transmission NEVER mix primate species in the same exhibit!

5.1.2. Measles

Measles is an RNA paramyxovirus related to canine distemper and rinderpest. Although measles is not considered a naturally occurring disease in NHPs, it is one of the most frequently reported viral diseases. Infection in NHPs occurs as a result of human contact, and then the infected primate can shed the virus, and re-infect man. Clinical signs in NHP can range from fever, conjunctivitis, coryza, bronchitis and Koplik spots on oral mucosa. A skin rash may appear on the third to seventh day and leukopenia is common. The virus may induce sever immunosuppression that can lead to the acquisition of opportunistic infections. Complications that may occur include otitis media, pneumonia, encephalitis, and enteritis. Measles infection in New World primates (marmosets, tamarins, and owl monkeys) is usually fatal and can be easily avoided by good husbandry practices and a vaccination program using an attenuated vaccine for both animals and staff.

5.1.3. Poxviruses

There are three genera of poxviruses that infect NHP: orthopoxviruses, yatapoxviruses and molluscipoxviruses. . They can infect numerous species of NHP and many have zoonotic potential. Infection of epithelial cells results in progression through stages characterized by proliferation, hydropic degeneration and umbilication resulting in the typical “pox” lesion.

  • Two orthopoxviruses (monkeypox and cowpox) can cause infection of NHPs resulting in typical cutaneous lesions and occasionally disseminated disease with death. These viruses are maintained by rodent vector reservoirs and may cause epizootics in NHPs. Both are zoonotic. Monkeypox, caused by Monkeypox virus, is serologically related to smallpox virus in humans. The disease is characterized by proliferate dermal ulcerations and vesicles. Adult monkeys may get fevers but death is rare except in infants. Because Monkeypox is serologically related to smallpox, it has the potential to be devastating in unvaccinated human populations. Recently an epizootic of cowpox has been described in common marmoset in a zoological collection in Europe. Infection resulted in a epizootic causing high morbidity and mortality and was related to transmission from rodent reservoirs

  • The yatapox grouping contains several serologically related viruses. Benign epidermal Monkeypox (BEMP) is a nonfebrile disease seen in macaques and is serologically related to the Yaba pox and Yaba-like pox viruses. It produces a typical proliferative epithelial lesion on the skin surface of the face and extremities. Yaba virus disease is seen in rhesus monkeys, baboons and rarely man. It appears as large subcutaneous, tumor like lesions that may undergo spontaneous regression.

  • Molluscum contagiosum is a benign epidermal proliferative disorder that has been described in human, horses and chimpanzees.

5.1.4. Rabies

Nonhuman primates housed in rabies endemic areas are as susceptible to rabies as man. In Brazil an enzootic form of rabies has established itself in common marmosets. Only killed vaccines or vaccines suitable for use in humans should be used to vaccinate NHPs.

5.1.5. Polio

All NHP are extremely susceptible to polio, especially the great apes. In areas where polio vaccination of humans is routine, this usually does not present a problem to these animals due to the lack of disease in the human population. Because of their heightened sensitivity to polio, all monkeys, especially the great apes, should be vaccinated for the disease as juveniles.

5.1.6. Hepatitis

The viral infectious hepatitis virus (Hepatitis A) has been identified in chimpanzees, patas, wooley monkey, gorilla, cebus, aotus, macaques and some tamarins. Antibodies to Hepatitis B (a lipid-enveloped DNA virus) have been reported in gibbons, chimps and baboons, but the status of natural infection is not known. All great apes should be considered to be at risk for this infection (vaccination with the human product is available). Hepatitis B is one of the more commonly reported blood-borne pathogens isolated in the human health care setting. Most human cases that have been contracted from NHPs have resulted from contact with young or recently imported chimps. No fatalities have been reported as a result of a zoonotic transmission of hepatitis.

Hepatitis C has been reported in chimpanzees and produces a chronic active hepatitis, cirrhosis and hepatocellular carcinoma.

5.1.7. Lymphocytic Choriomeningitis Virus (LCMV)

This rodent virus has been determined to be the cause of Callitrichid hepatitis. It presents as acute onset of lethargy, anorexia and elevated liver enzymes. There is high mortality associated with this infection in captive collections. Monkeys are thought to get this infection from mice in the exhibit, or from being fed pinkie mice as treats in their diet. This practice should be avoided. Other potential sources include exposure to infected feral rodents in a naturalistic setting. LCMV is a potential zoonotic concern and has been transmitted to human handlers.

5.1.8. Filoviruses

Filoviruses belong to the family Filoviridae, one of several groups of viruses that can cause hemorrhagic fever in animals and humans. Marburg virus was the first filovirus to be discovered in 1967 in a shipment of African green monkeys imported into Marburg, Germany. There were 31 human cases associated with this outbreak and 7 of those were fatal. Then in 1976, Ebola virus was recognized in Zaire. Ebola virus has now been subtyped into these four distinct viral groups: Zaire, Sudan, Ivory Coast, and Ebola-Ralston. These relatively newly recognized strains of filoviruses have been given special attention due to a viral outbreak in a Virginia quarantine facility in recently imported cynomolgus monkeys (Ebola-Reston). No filovirus-related illness was observed in any humans who had been in contact with these infected monkeys, but antibody titers were detected, indicating transmission did occur. The three subtypes that are known to cause disease in humans are Ebola-Zaire, Ebola-Sudan and Ebola-Ivory Coast. The disease is called Ebola Virus Hemorrhagic Fever and clinical signs in both humans and NHP are: fever, chills, headaches, muscle aches, and anorexia. As the disease progresses, vomiting, diarrhea, abdominal pain, sore throat, and chest pain may develop. A coagulopathy then develops and bleeding may occur from injection sites as well as into the gastrointestinal tract, skin, and internal organs. Because of the high mortality rate from human filovirus infections (Ebola, Marburg-Europoe, Sudan and Zaire strains), the CDC has updated regulations and inspections of imported primates. Recent evidence has shown that wild primates, especially the great apes, may be susceptible to naturally occurring Ebola outbreaks in Africa. Current outbreaks are severely threatening key populations of lowland gorillas in central Africa (see CM Challenge ).

5.1.9. Retroviruses

There are two groups of retroviruses that are endemic in human populations, the human T cell leukemia / lymphotropic viruses (HTLV) types I and II and the human immunodeficiency viruses (HIV) types 1 and 2. Non-human primates are the natural hosts for a variety of retroviruses including viruses in the betaretrovirus, gammaretrovirus, deltavirus, lentivrus and spumavirus genera. All of these viruses cause life long infections in non-human primates and may be transmissible through sexual contact, blood, bodily fluids or breast milk. Genetic analysis of primate retroviruses indicates that cross species transmission has occurred repeatedly on an evolutionary time scale. Endogenous retroviral sequences are common and transmissions have produced significant selective pressure on populations often leading to positive selection of host restriction factors.

Simian retroviruses represent a significant zoonotic risk to humans.. In 1993, the CDC and the National Institutes of Health implemented a voluntary testing and counseling surveillance program for SIV following detection of SIV in a worker at a primate facility. This study was later expanded to include voluntary testing and counseling for exposures to SFV, STLV, and simian type D retroviruses. There are significant implications for laboratory workers and zoo personnel that work with NHPs.

Primate Retroviridae

Orthoretrovirinae

Primate virus

Zoonotic potential

  • Alpharetrovirus

none

  • Betaretrovirus

Type D retroviruses

Yes

  • Gammaretrovirus

Gibbon ape leukemia virus/others

Unknown

  • Deltaretrovirus

Primate T cell leukemia group

Yes

  • Epsilonretrovirus

none

  • Lentivirus

Simian immunodeficiency viruses

Yes

  • Spumavirinae

  • Spumavirus

Simian foamy viruses

Yes

Simian Immunodeficiency Virus

  • SIVs are lentiviruses, morphologically similar and biologically related to HIV-1 and HIV-2. SIV can cause acquired immunodeficiency syndrome (AIDS) - like illnesses in susceptible macaque monkeys and when it crosses from host-specific species natural host to non-natural host species.

  • These viruses cause widespread infection of many African species of NHP but not Asian species or new world primates. SIV strains are not usually pathogenic in their natural host species.

  • Presently monkeys with SIV are used extensively in the study of AIDS. SIV is genetically and antigenically related to HIV-2, resulting in substantial serological cross-reactivity. All of the simian immunodeficiency viral isolates have characteristics in common with HIV, including genomic organization and some serological cross reactivity Immunodeficiency results from progressive loss of CD4 T cells and results in reactivation of latent infections or acquisition of environmental and other opportunistic pathogens. Common AIDS defining clinical diseases include wasting, CMV, LCV lymphoma, Pneumocystis pneumonia, Cryptosporidia and Mycobacterium avium and closely paraellel the spectrum of diseases observed in human patients.

  • Evidence of SIV infection has been reported for over 30 different species of African nonhuman primates (see table 3). Two of these viruses, SIVcpz from chimpanzees and SIVsm from sooty mangabeys, have been shown to be the source of HIV1 and HIV2 and acquired immunodeficiency syndrome (AIDS) in humans. The relationship between simian retroviruses and the disease in humans is a great concern, especially with the recent increase in the Bushmeat Trade . Blood donation and organ donation research is also concerned with possible transmission of these viruses. There have been at least nine documented cases of humans infected with SIV (Hahn, et. al).

Table 3: Simian retrovirus infection of various nonhuman primate species

(Primate nomenclature is as described by Groves, infection determined by presence of cross-reacting antibodies, virus isolation, and/or retroviral sequences)

Genus

Primate species

Common name

Retroviruses1

Old World Monkeys

Papio

P. anubis

P. cynocephalus

P. papio

P. hamadryas

P. ursinus

olive baboon

yellow baboon

Guinea baboon

hamadryas baboon

chacma baboon

SFV, STLV

SFV, STLV, SIV2, SRV

SFV, STLV

SFV, STLV

SFV, STLV, SIV2

Theropithecus

T. gelada

gelada baboon

SFV, STLV

Mandrillus

M. sphinx

M. leucophaeus

mandrill

drill

SFV, STLV, SIV

SFV, STLV, SIV

Lophocebus

L. albigena

grey-cheeked mangabey

SFV, SIV

Allenopithecus

A. nigroviridis

Allen's swamp monkey

SFV, STLV, SIV

Cercocebus

C. galeritus

C. torquatus

C. atys

C. a. lunulatis

C. agilis

C. chrysogaster

Tana River mangabey

red-capped mangabey

sooty mangabey

white-crowned mangabey

agile mangabey

golden-bellied mangabey

SFV

SFV, STLV, SIV

SFV, STLV, SIV

SIV2

SFV, STLV, SIV

SFV

Miopithecus

M. talapoin

M. ougouensis

Angolan talapoin

Gabon talapoin

SFV, SIV, SRV

STLV, SIV

Erythrocebus

E. patas

patas monkey

SFV, STLV, SIV2

Chlorocebus

C. pygerythrus

C. sabaeus

C. aethiops

C. tantalus

vervet

African green monkey

grivet tantalus

SFV, STLV, SIV

SFV, STLV, SIV

SFV, STLV, SIV

STLV, SIV

Cercopithecus

C. albogularis

C. mitis

C. lhoesti

C. solatus

C. cephus

C. erythrotis

C. ascanius

C. neglectus

C. mona

C. lowei

C. campbelli

C. denti

C. pogonias

C. diana

C. nictitans

C. hamlyni

Sykes's monkey

blue monkey

L'Hoest's monkey

sun-tailed monkey

mustached guenon

red-eared guenon

red-tailed monkey

De Brazza's monkey

mona monkey

Lowe's monkey

Campbell's mona

Dent's mona

crested mona

Diana monkey

greater spot-nosed monkey

Hamlyn's monkey

SFV, STLV, SIV

STLV, SIV

SFV, SIV

SIV

SFV, STLV, SIV

SIV

SIV

SFV, SIV

SFV, STLV, SIV

SIV

SFV, SIV

SIV

SFV, STLV, SIV

SFV, SIV

SFV, STLV, SIV

SIV

Colobus

C. guereza

mantled guereza

SFV, SIV

Piliocolobus

P. badius

western red colobus

STLV, SIV

Procolobus

P. verus

olive colobus

SIV

Macaca

M. mulatta

M. nemestrina

M. fascicularis

M. arctoides

M. radiata

M. fuscata

M. silenus

M. sylvanus

M. tonkeana

M. cyclopsis

M. nigra

M. maura

M. nigrescens

M. ochreata

rhesus macaque

pig-tailed macaque

cynomolgus macaque

stump-tailed macaque

bonnet macaque

Japanese macaque

lion-tailed macaque

Barbary macaque

tonkean macaque

Formosan rock macaque

Celebes crested macaque

moor monkey

Gorontalo macaque

booted macaque

SFV, STLV, SRV

SFV, STLV, SRV

SFV, STLV, SRV

SFV, STLV

SFV, STLV, SRV

SFV, STLV, SRV

SFV

SFV, STLV

STLV, SRV

STLV, SRV

SFV, STLV

STLV

STLV

STLV

Pygathrix

P. nemaeus

red-shanked douc

SFV

Trachypithecus

T. francoisi

T. obscurus

Francois's langur

spectacled langur

SFV

SRV

Semnopithecus

S. entellus

northern plains gray langur

SRV

Old World Apes

Hylobates

H. pileatus

H. leucogenys

H. lar

H. syndactylus

pileated gibbon

northern white-cheeked gibbon

white-handed gibbon

Siamang

SFV

SFV

GALV

STLV

Gorilla

G. gorilla gorilla

western gorilla

SFV, STLV, SIV

Pan

P. paniscus

P. troglodytes

bonobo or pygmy chimpanzee

chimpanzee

SFV, STLV

SFV, STLV, SIV

Pongo

P. pygmaeus

P. abelii

Bornean orangutan

Sumatran orangutan

SFV, STLV

SFV, STLV

Old World Prosimians

Otolemur

O. crassicaudatus

brown greater galago

SFV

New World Primates

Ateles

A. species

spider monkey

SFV

Cebus

C. species

capuchin

SFV

Saimiri

S. sciureus

squirrel monkey

SFV,

Callithrix

C. jacchus

common marmoset

SFV

Cacajao

C. species

uakari

SFV

Lagothrix

L. lagothrica

wooly monkey

SSV

1SFV, simian foamy virus; SIV, simian immunodeficiency virus; STLV, simian T-lymphotropic virus; SRV, type D retrovirus; GALV, gibbon ape leukemia virus; SSV, simian sarcoma virus

2Monkey-to-monkey cross-species infection.

Foamy Viruses (Spumavirus genus of Retroviridae : SFV or Simian Spumaviruses)

  • SFVs are common in captive NHPs; greater than 95% of captive macaques over 3 years of age are seropositive.

  • Spumaviruses differ from other retroviruses in several respects including the viral polymerase gene is expressed from a spliced sub-genomic RNA and the extracellular particle contains large amounts of reverse-transcribed DNA. Presently there are seven distinct SFVs including SFV-1 in rhesus macaques, SFV-3 in African green monkeys and SFV-6 in chimpanzee and SFV-7 in NWPs

  • SFV can be readily isolated from infected animals saliva or from peripheral blood lymphocytes and it has been isolated in approximately 3% of tested laboratory and zoo workers with NHP exposure.

  • To date, there have been no ill effects to health in either the humans that are positive for SFV or the positive NHP. This virus has been referred to as the virus in search of a disease, because it does have the capacity to incorporate itself into DNA and is routinely transmitted between NHP without signs of disease.

Simian Retrovirus

  • Type D retroviruses have been documented to cause a form of chronic immunodeficiency disease in several macaque species, including the natural hosts.

  • 0 - 90% of Asian macaques can be infected in a collection

  • The virus has wide tropism for epithelial cells, macrophages, B cells and T cells causing a pancytopenia in peripheral blood.

  • Diarrhea and wasting are the most common clinical signs

  • Opportunistic infections such as Retroperitoneal fibromatosis, Noma, Rhodococcus equi and CMV may occur

  • Both an antibody positive/viremic negative and antibody negative/viremic positive state are observed; a combination of serology and PCR or viral isolation must be used for definitive diagnosis.

  • Infection has also beendescribed in Hanuman langurs (Semnopithecus entellus) and baboons (Papio cynocephalus) but not associated with clinical disease.Simian retrovirus is a serious health threat to captive bred populations of macaques and potential confounder of experimental work.

Talapoin monkeys Miopithecus talapoin
Talapoin monkeys Miopithecus talapoin

Simian T-cell Lymphotropic Virus type 1

  • STLV1 and STLV2 share an extensive genomic sequence with human T-lymphotropic virus type 1 and 2 (HTLV1, 2) and are associated with T-cell lymphomas in non-human primates.

  • They are also largely nonpathogenic in natural hosts

  • Cross species transmission has resulted in epizootics of malignant lymphoma in captive colonies of baboons.

  • There is a 0-95% seroprevalence in susceptible captive and wild populations

5.1.10. Other Zoonotic viruses

  • Parainfluenza viruses

  • Mumps

  • Respiratory Syncytial Virus

  • Rotavirus

  • Poliovirus

  • Coxsackievirus

  • Rhinovirus

  • Simian virus 40

5.2. Bacterial Zoonoses

5.2.1. Mycobacterial Spp.

Mycobacteria are responsible for tuberculosis, an increasingly rare disease in captive primates. Old world species of primates appear to be more susceptible than New World species. Historically, the three major species of Mycobacteria - avium, bovis, and tuberculosis, have been incriminated as causing disease in NHPs. Recently, there have also been reports of other atypical mycobacteria in NHPs. The primary route of transmission is through inhalation or ingestion.

M. tuberculosis
M. tuberculosis

Clinical disease can be hard to detect until the disease is in advanced stages. Clinical tuberculosis causes severe weight loss, lethargy, and coughing and is almost always fatal in NHP. In both humans and NHPs the skin test detects only mycobacterial infection, not active disease. Active disease is diagnosed either by recovery of the organisms in culture or by thoracic radiographic lesions consistent with active TB. PCR and other amplification tests can also detect organisms but the sensitivity of PCR for the detection of latent infection is not well established. Newer assays have been developed that measure cell mediated (Primagam ®) and humoral (Stat-pak ®) immune responses. Treatment of positive, clinical NHP is highly effective but is generally not advised at this time due to both the fear of developing resistant strains of Mycobacteria as well as the risk to human handlers. All owners of NHP and others having contact with them, including veterinary staff, should be TB tested annually and if positive, should receive treatment under the guidance of a TB specialist.

5.2.2. Pseudotuberculosis

Yersinia pseudotuberculosis is a zoonotic, infectious bacterial agent that has a worldwide distribution and is endemic in European countries. The infection can affect a wide range of host species but in particular has caused numerous deaths in tamarins, marmosets and Goeldi's monkeys in captivity. Clinical signs of infection can range from asymptomatic animals that shed the bacteria, to nonspecific signs of systemic or enteric diseases or sudden death that may be difficult to diagnose. This disease can also produce a wasting syndrome. The organism can live in the soil for long periods of time and asymptomatic animals, combined with the difficulties in culturing the organism from rectal or fecal swabs, can all lead to difficulties in controlling the organism. Preventative measures such as quarantine, good sanitation, good hygiene, especially in food preparation, and pest control, together with a vaccination program in endemic areas, are all recommended in preventing infection, although vaccination is not 100% effective.

5.2.3. Bacterial Meningitis Syndrome

This syndrome seen in great apes has many etiologic agents and may be zoonotic depending on the agent involved. The syndrome can present as either acute or chronic meningitis and prompt, effective diagnosis and treatment is required to avoid fatalities or chronic, persistent clinical impairments. The most prevalent pathogens implicated are Streptococcus pneumoniae, Neisseria meningitides, and Hemophilus influenza type B.The N. meningitides and H. influenza type B are threats to exposed humans.

5.2.4. Campylobacter jejuni

Campylobacter jejuni is a common fecal bacterium found in old and new world monkeys. Asymptomatic shedding of large numbers of bacteria in feces is common. Some monkeys may exhibit mild to severe diarrhea accompanied by weight loss, dehydration and bloody feces. The disease in humans may cause debilitating diarrhea and people may also shed the bacteria asymptomatically.

5.2.5. Shigellosis

Shigellosis or bacillary dysentary is common among old world monkeys. The most common species cultured in old world monkeys is Shigella flexneri, while the most common isolate from humans is S. sonnei. In most cases of zoonotic transmission humans are the reservoir for NHP infections. Shigella is very contagious to humans and children are very susceptible. Diarrhea with blood and mucus is the most common clinical sign in both humans and NHP. Shigella, if left untreated, may be rapidly fatal to NHP and human children. Most strains are susceptible to enrofloxacin.

Shigellosis
Shigellosis

Shigella
Shigella

5.2.6. Other Bacteria

Yersinia enterocolitica, Salmonella, and E. coli all can also be cultured from the GI tract of NHPs and are capable of causing zoonotic disease in humans. These organisms may or may not be associated with clinical disease in NHPs and one negative culture does not indicate a disease free animal.

5.3. Parasitic Zoonoses

5.3.1. GI parasites

5.3.1.1. Protozoan parasites

Giardia lamblia, Cryptosporidium, Enterocytozoon bieneusi, Balantidium coli, and Entamoeba histolytica are all intestinal protozoa that can infect monkeys and humans. Diarrhea in both monkeys and humans can range from mild to severe. There have been a few documented cases of fatalities in neonatal and juvenile monkeys due to these protozoa.

Toxoplasmosis gondii can be potentially devastating with high mortality and permanent neurological problems in surviving animals in naïve populations of Prosimians and NWPs. All exposure to cat feces, undercooked and raw meat should be avoided. Cockraoches may serve as mechanical vectors and NHPs may be infected through ingestion of tissue cysts in rodent vectors.

5.3.1.2. Metazoan parasites

There are also many nematode parasites seen in NHP. Some of the most frequently seen are Oesophagostomum, Strongyloides, and Dipetalonema species. Other GI parasites sometimes seen are Hymenolepis nana, Echinococcus granulosus and Prosthenorchus elegans.

P. elegans Acanthocephalans or thorny headed worms are parasites of the intestine of a variety of NHPs. P. elegans is the most commonly recognized parasite and found naturally in central and south America. Infection may be asymptomatic or associated with diarrhea. In severe cases infection is associated with anorexia and weight loss. If perforation occurs, animals may die acutely. Eggs are passed in the feces and the ex vivo development leads to the maturation of an infective cystacanth. An intermediate Cockroach host is required for completion of the life cycle. P. elegans is found primarily in the colon and cecum and P. spirula is found in the ileum. Infection is associated with a granulomatous colitis. At the attachment site there is usually extensive fibrosis and granulomatous inflammation. The proboscis perforates through the mucosa and submucosa and may occasionally perforate the colon wall resulting in a suppurative peritonitis. Grossly the parasites are recognized as stout pale white to tan parasites found near the ileal cecal junction usually in association with a transmural colitis. Preventative anthelmintics as well as diligent fecal screens and cockroach control are critical in maintaining these animals.

Prosthenorchis elegans
Prosthenorchis elegans

Pest control is key to the health of captive non-human primates!

5.3.2. Blood borne parasites

Blood borne parasites are rare in captively bred monkeys but may be seen in wild caught monkeys.

5.3.2.1. Trypanosoma cruzi

Trypanosoma cruzi has been isolated from recently imported and domestic squirrel monkeys, tamarins, marmosets and macaques and causes Chagas' disease. This is a disease that causes debilitation and cardiomyopathy in man. Diagnosis may be difficult and animals may remain infected for prolonged periods.

5.3.2.2. Primate malaria (Plasmodium sp.)

Malarial infections are frequent in some species of imported old and new world species. These infections are usually asymptomatic in the natural host but may cause disease when animals are stressed or treated with immune modulatory drugs. Cross species transmission may result in severe and life threatening disease. Many plasmodium species that naturally infect NHPs have been proven to infect humans as well. Plasmodium knowlesi, a parasite of cynomolgus and pig-tailed macaques, is an emerging disease in human populations of Southeast Asia.

The above listing of zoonotic diseases of NHPs is greatly abbreviated. For more information on these diseases, please refer to the author's references. The most important point in any discussion of NHP zoonotic disease is the idea of disease prevention. This is the key to maintaining both healthy NHPs and minimizing the risk to pet owners and veterinary staff. Veterinarians who chose to treat NHPs should handle them as a high zoonotic risk. Protection from blood-borne pathogens, respiratory pathogens, gastrointestinal, and cutaneous diseases must be instituted. All staff handling both the animal and its biological products must be well educated in the risks they are taking and in the ways of disease prevention. The NHP owner must also be aware of the risks to both humans who have contact with the animal and also the risks to the animal from the contacted humans.

Rhesus Macaque
Rhesus Macaque

6. Emerging and re-emerging infectious diseases of nonhuman primates

Elimination of infectious diseases from NHP colonies has proven difficult for many reasons and infectious diseases continue to seriously impact wild populations. Factors that promote emergence and re-emergence of infectious diseases are often anthropogenic and include: 1) importation of primates from sources with poor microbial quality control; 2) transmission of infectious agents from human contacts; 3) habitat destruction; 4) introduction of disease vectors; and 5) and cross species transmission of agents from other primate and non-primate species. Two excellent texts that examine the impact of infectious diseases on primate (human and NHP) evolution and ecology are:

  • Infectious Diseases in Primates, behavior, ecology and evolution, CL Nunn and S. Altizer Oxford Series in Ecology and Evolution, 2006

  • Human Frontiers, Environments and Disease, past patterns, uncertain futures, T Michael Cambridge University Press, 2001

NHP often harbor agents for which there has been a long period of host pathogen co-evolution. In these instances infection is in general asymptomatic and overt disease rare. In contrast such co-evolutionary adaptations are lacking following cross species transmission of agents and as a result are often associated with severe disease outcomes. Numerous examples exist of the adverse effect cross species transmission can have on captive and wild populations of NHPs. Epizootic die-offs resulting from Ebola virus transmission to Gorillas and Chimpanzees populations in Minkebe forest of Gabon have been well documented. Similarly Yellow fever Virus infection in neotropical primates results in epizootics with high morbidity and mortality. Further research is needed to determine the impact of infectious diseases on primate conservation. The potential impact of cross species transmission should also be considered when designing zoological exhibits and implementing NHP housing strategies. While free ranging primate exhibits have many benefits, it should be recognized that potential exposure to infectious agents from environmental sources and other wild or captive animals may be increased.

Emerging and re-emerging infectious agents of NHPs.

Setting*

Affected species

Zoonotic potential†

Cross species

Bacterial

Mycobacterium tuberculosis

L, Z, W

OWP/NWP

Y

Y

Atypical mycobacteria

L, Z

OWP/NWP

N

N

Enteropathogenic E. coli

L

OWP/NWP

Y

N

Clostridium piliforme

L

OWP/NWP

N

U

Bacillus anthracis

W

OWP

Y

N

Klebsiella pneumoniae

L, Z

NWP

U

N

Helicobacter spp.

L, Z

OWP/NWP

Y

U

Bartonella quintana

L

OWP

Y

Y

Viral

West Nile virus

L, Z

OWP

Y

Y

Measles virus

L, Z

OWP/NWP

Y

Y

Simian varicella virus

L

OWP

N

N

Simian parvovirus

L

OWP

Y

N

Cynomolgus polyoma virus

L

OWP

U

N

Hepatitis A, E

L, Z, W

OWP/NWP

Y

Y

GB virus A

L, Z, W

NWP

N

N

Cowpox

Z

NWP

Y

Y

Herpes simplex

Z

NWP

Y

Y

RRV/RHFV

L

OWP

N

N

Hepatitis B virus

W, Z

OWP

Y

Y

Ebola virus

W

OWP

Y

Y

Simian immunodeficiency viruses

Z, W

OWP

Y

Y

Parasitic

Plasmodium spp.

L, Z, W

OWP/NWP

Y

Y

Babesia microti

L

OWP

Y

Y

Enterocytozoon bieneusi

L

OWP

Y

U

Encephalitozoon cunniculi

Z

NWP

Y

Y

Acanthamoeba sp.

L, Z, W

OWP

Y

N

*L, laboratory primates; Z, zoological collections; W, wild primate populations; OWP, Old World Primates; NWP, New World Primates

†Y, yes; N, No

7. Preventative Care/Restraint/Anesthesia and Handling

Veterinarians who elect to see NHP in their veterinary practice also have a responsibility to become educated in the specialized needs of NHP. The most critical of these concerns is becoming familiar with zoonotic diseases of NHP and how to handle the NHP in order to screen for these diseases without unduly endangering the animal, the owner, staff, and other patients and owners.

The examination room should be equipped with securely locking doors and escape proof, locked windows. The counters should be cleared and everything needed for the examination (capture nets, primate gloves, towels, squeeze cage, sedative dose drawn up) should be placed in the room before the NHP enters the room. Once the NHP is in the room the doors should not be opened again until the primate is properly restrained. Many NHPs are excellent escape artists and this skill should not be taken lightly.

7.1. Primate Bite / Wound Kit

Bite kit
Bite kit

Aggression
Aggression

Working with NHPs is inherently dangerous due to zoonotic diseases and the risk of animla associated injuires. NHPs are fast, strong and highly intelligent animals that may quickly and unexpectedly cause severe injuries in other animals or human contacts. A wound kit should be well marked, readily accessible and stocked with

  • An antiseptic skin cleanser

  • A sterile ophthalmic cleansing soln (Dacriose)

  • Lodophor surgical scrub

  • Disposable latex gloves

  • Sterile gauze and irrigation syringe

  • Sterile bowl

  • Safety glasses/face shield

  • Phone numbers and directions to local emergency rooms

  • Step by step instructions.

Wounds should be scrubbed vigorously with an antiseptic cleanser first and flushed with running water for 15 minutes. Loosely cover the wound and proceed to emergency room. For eye splashes, irrigate the eye with clear water or Dacriose for a full 15 minutes before proceeding to the emergency room. The animal involved should also be identified and appropriate testing done to determine any zoonotic risks.

Human Health Recomendations:

All NHP owners or handlers, including veterinarians and staff should participate in occupational health and safety program administered by a health care professional experienced with NHPs. Such a program should include:

  1. TB testing at least annually, thoracic radiographs or treatment if TB positive

  2. Pre-exposure serum banking

  3. Vaccinations based on risk assessment for rabies, tetanus, polio, and measles/rubella.

  4. Training in zoonotic diseases and use of personal protective equipment

All Personnel handling nonhuman primates should wear personal protective equipment based on risk assessment of the species and individual animal. This may include:

  1. Disposable gloves

  2. Kevlar or leather gloves

  3. leather gauntlets and arm protectors

  4. Protection of mucous membranes; safety glasses and face shield or goggles; face mask

  5. Respiratory protection when warranted by task based risk assessment; most commonly N95 respirator or PAPR

Proper protection during field work may be particularly challenging due to lack of water, electricity and environmental conditions (heat, humidity). Fatal zoonotic disease has been documented following in an individual following a field necropsy. Planning is required to make sure adequate personal protective equipment and post exposure and first aids supplies are available. If possible, work in a well-ventilated area that has UV exposure and air exchanges >15/hour. Careful hand washing is mandatory, regardless of glove usage. All accidents/injuries involving animals, animal wastes, or potentially contaminated equipment must be dealt with promptly.

Staff education is a MUST and is the responsibility of the veterinarian. Equally important is education of NHP owners about the risks to themselves and their pets. Complete necropsies should always be done in the event of an animal death to rule out potential unknown health risks to caretakers and owners.

7.2. Routine Health Care

The veterinarian should examine non-human primate pets at least once a year, preferably twice a year. Exams should consist of detailed physical examinations including a thorough dental exam, annual TB tests, parasite exams (both direct and indirect ova detection), complete blood counts, serum biochemistries.Radiographs, and appropriate viral screens should be considered on a case by case basis. Vaccinations differ depending on the age and type of NHP (old world vs. new world). In order to responsibly and safely examine these pets, some specialized training and education of veterinary staff, as well as clinical adaptations, should be made.

Routine Primate Physical Examination

  • Complete history (permits / origin ) and direct observation of the animal in its home environment

  • Thorough physical exam (anesthesia if >3-5 kg BW)

  • Dental exam

  • Complete blood count and serum biochemistry

  • Fecal exam: direct, float, fecal centrifugation and/or antigen capture

  • Fecal cultures: Salmonella, Shigella, Campylobacter, Yersinia

  • TB test

  • Radiographs

  • Appropriate viral screens

While chemical restraint is often used, direct visual observation of the animal in its environment is the single most important component of the physical exam. The type of restraint used for routine procedures will vary greatly depending on the size, health and temperament of the NHP, the NHP owner, and the clinical setting. Any time a NHP is handled, appropriate protective equipment should be used. Whenever possible, chemical restraint should be used to minimize the risk of injury and zoonotic disease to the handlers, veterinarian and non-human primate.

Baby Gorilla
Baby Gorilla

7.2.1. Vaccination recommendations for NHP

Vaccination recommendations should be based on risk assessment following review of the species of primate, housing conditions and previous disease history.

Disease

Vx Schedule

Severity

Efficacy

Adverse Reactions

Vx Recommendations

Tetanus

2 mo, 4 mo, 6 mo, 18mo, 4-6 yrs, 14-16 yrs, every 10 yrs after

Can be fatal

High

Numerous

All species

Poliomyelitis

2 mo, 4 mo, 6 mo, 18 mo, 4-6 yrs, 14-16 yrs

Inapparent to fatal

High

None reported

Yes/ Great apes

Measles

15 mo, 10-12 yrs

Inapparent to fatal

High

None reported

All species

Hemophilus

2 mo, 4 mo, 6 mo, 18 mo

Mild to fatal

Unknown

Few

Limited

Rabies

16 weeks, annually after that

Fatal

High

Few

All in endemic areas

Hepatitis B

2 mo, 4 mo, 6 mo

Mild to fatal

Unknown

Few

Great apes

Mumps

15 mo, 10-12 yrs

Mild to fatal

Unknown

Few

Great apes

7.2.2. TB testing

TB testing in a ring-tailed lemur
TB testing in a ring-tailed lemur

The recommended method of tuberculin testing is to use 0.1 ml of mammalian old tuberculin approved by the USDA.). A 25 to 27 gauge, 1/2 needle is used to inject the tuberculin intradermally, usually in the upper eyelid. The nipple can be used as a secondary confirmatory site. The test should then be read at 24, 48, and 72 hours. Any reaction should be considered positive and the animal should be immediately quarantined until further diagnostics can be done. These diagnostics may include radiographs, sputum, fecal and blood cultures, gastric lavage for cytology and culture. A number of new assays are available included PCR detection of pathogen nucleic acid and detection host cell mediated (Primagam ®)and humoral (Stat-pak®) responses to mycobacterial antigens. The sensitivity and specificity of these assays is not well established.

Scoring of intradermal skin test

Recorded at 24, 48 and 72 hours

Grade 1 -slight bruising of eyelid (negative)

Grade 2 -erythema of eyelid without swelling (negative)

Grade 3 -varying degrees of erythema with minimal swelling (indeterminant)

Grade 4 -obvious swelling with dropping of eyelid (positive)

Grade 5 -marked swelling and/or necrosis of eyelid (positive)

Positive TB test
Positive TB test

Testing of NHPs for M. tuberculosis

Intradermal skin test

Primagam

Stat-Pak

Commercial source

Synbiotics

Prionics

Chembiodiagnostics

Product availability

intermittent

intermittent

Good

Immune response detected

DTH

CMI (IFN)

Antibody response

Utility in NWPs

++

+/-

unk

Sample

n/a

Heparinized WB

WB, Serum, plasma

Antigen

Purified complex

(M. tuberculosis)

Purified complex

(M. bovis/avium)

Recombinant

(ESAT-6/CFP10 hybrid, MPB83, and TBF10)

Result

Subjective (0-5 scale)

Objective (O.D.)

Objective (+/-)

Laboratory equipment

none

ELISA plate reader

none

Time before results

72 hours

>36 hours

<30 minutes

Duration before test can be repeated

2 weeks

0

0

Sensitivity during early infection

++

++

+

Sensitivity late or latent infection

-

+/-

++

Cross reactivity with atypical mycobacteria

yes

Yes (assay designed to distinguish)

minimal

Sensitivity

Specificity

+84%

+++ (87%?)

++68%

++ (97-100%?)

+++90%

+ (98.5%)

7.3. Mechanical Restraint and Handling

Lemur
Lemur

7.3.1. For non-human primates weighing <12 kg

A squeeze cage, where either the back or front is moveable and able to squeeze the primate against the bars for easy injection, is preferable. Not many veterinary clinics have these cages available, although if a large percentage of clients own NHP as pets, they are well worth the investment. If no squeeze cage is available and hand restraint is use, at least one handler, plus the veterinarian, is needed for adequate restraint. The owner of the primate should not be one of the handlers. For a physical examination, the primate should be firmly grasped from behind, just proximal to the elbows. The arms should be gently rotated so that the elbows are almost touching behind the animals back. Excessive force may result in fractures, especially in severely debilitated and undernourished animals. Once the arms have been properly restrained, the ankles should be grasped and the legs extended until the NHP is in a stretched position.

7.3.2. For non-human primates weighing 12 - 15 kg

At least two handlers are needed. It is very important to never underestimate the strength of these animals. Heavy leather gloves may be worn, although restraint may be difficult with these on and they may provide a false sense of security. Many NHP have penetrated such gloves with their teeth. The use of nets, grab poles and rabies poles may be sufficient to give the veterinarian time to quickly inject the NHP with a tranquilizer. Non-human primates are very intelligent and have been known to grab syringes and redirect them towards the handler or veterinarian! They also have a tremendous memory and what works once, may not work again.

7.3.3. Animals over 15 kg

Unless severely debilitated, should be chemically restrained in order to prevent human injury.

Gorilla recovering from anesthesia
Gorilla recovering from anesthesia

To view NIH video see http://grants1.nih.gov/grants/olaw/TrainingVideos.htm#primate

7.4. Chemical Restraint and Anesthesia

(see dosages below in table 4)

Gorilla receiving oral medication
Gorilla receiving oral medication

Orangutan
Orangutan

7.4.1. Preoperative Assessment and Considerations

Nonhuman primates should receive a physical exam before anesthesia, as health status can influence anesthetic outcome. Prior to anesthesia, the complete clinical and experimental history should be reviewed. The preoperative evaluation may include blood work or other diagnostics depending on medical history, clinical condition, and the procedure to be done. Abnormalities such as anemia or hypoproteinemia may require treatment or intraoperative support.

7.4.2. Fasting

Nonhuman primates are fasted to reduce the risk of pulmonary aspiration of gastric contents. Old World species are routinely fasted for 12 hours prior to surgery. It may be desirable to remove shavings or other substrate from the cage to prevent ingestion of foreign material after food is removed. Smaller primates may become hypoglycemic if fasted for long periods; food is withheld from New World species for 6-8 hours. Water is generally available ad libitum.

7.4.3. Equipment

Standard small animal veterinary anesthesia equipment is used for most nonhuman primates. Precision vaporizers are used for the delivery of inhalant anesthetics. A non-rebreathing circuit such as a Bain circuit can be used for animals weighing less than 2 kilograms. When inhalant anesthetics are used, a gas scavenging system is essential. Mechanical ventilation can be provided for larger primates with a standard small animal ventilator. A wide variety of veterinary and human monitoring equipment is available to monitor cardiac and respiratory parameters, electrocardiogram, pulse oximetry, capnography, temperature, and inspired/expired gases during anesthesia. Depending on the size of the patient, human infant or pediatric sensors may be needed for monitoring equipment. Proper functioning of anesthesia equipment and an uninterrupted supply of oxygen should be ascertained before each use. Figure 1 depicts anesthetic equipment used for nonhuman primates.

Anesthesia
Anesthesia

7.4.4. Preparation

Endotracheal intubation maintains the airway during general anesthesia. Commercially available cuffed endotracheal tubes can be used in Old World primates. Small cuffed or uncuffed tubes can be used in New World species. Smaller species can be intubated with tubes constructed from 8 Fr infant feeding tubes. The tube should terminate anterior to the tracheal bifurcation. Lidocaine gel or liquid is used to prevent laryngospasm.

Patient care during anesthesia should also include prevention of hypovolemia and hypothermia. Placement of a peripheral venous catheter allows for intraoperative delivery of maintenance fluids (20 ml/kg for the first hour, then 10 ml/kg/hr) and provides venous access for emergency drugs. A bland ophthalmic ointment should be applied to protect the corneas from desiccation.

7.5. Premedications

Anesthetic premedications are often used to facilitate induction, reduce the dose of subsequent anesthetics, decrease the incidence of adverse events during anesthesia, and begin the process of postoperative pain management.

7.5.1. Anticholinergics

Anticholinergics are often used as premedications in nonhuman primates. Atropine (0.02-0.05 mg/kg IM) decreases salivary and bronchial secretions and reduces bradycardia. The duration of effect in most primate species is approximately an hour. Atropine reduces bradycardia associated with administration of xylazine or fentanyl. Because cardiac output in pediatric nonhuman primates is dependent on heart rate, bradycardia is of clinical significance in these patients. Glycopyrrolate (0.005-0.01 mg/kg IM) has a more potent antisialogogue effect than atropine and longer duration of action.

7.5.2. Preemptive Analgesia

As discussed below, postoperative management of pain is an important component of any anesthetic regime. Preemptive analgesia has been shown to reduce the amount of general anesthesia required and speed recovery and return to function by significantly reducing postoperative pain. Preemptive analgesia should be considered in drug selection and may reduce the dose of subsequent drugs used.

7.6. Injectable Anesthetics

Injectable anesthetics are useful in nonhuman primates because these agents can often be administered intramuscularly while the animal is restrained manually or with the squeeze-back mechanism of the cage. As with other anesthetics, the health and physical status of the animal will impact the safe and effective dose.

7.6.1. Ketamine

Ketamine is a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor and acts by functionally disrupting neuronal pathways in the central nervous system. A functional cerebral cortex is required for the anesthetic actions of ketamine. It is metabolized by the liver and eliminated in the urine. Ketamine has a wide margin of safety and is well-tolerated in nonhuman primates. It can be used alone or in combination with other anesthetic agents. Ketamine produces a state of catalepsy and analgesia without muscle relaxation. A dose of 5-25 mg/kg IM produces effects within 2-6 minutes; the duration of effect is dose-dependent, but usually 20-60 minutes is observed. Palpebral, laryngeal, and pharyngeal reflexes are maintained. Ketamine produces minimal cardiorespiratory effects in nonhuman primates. Ketamine did not cause significant changes in heart rate, mean arterial pressure, respiratory rate, arterial PO2, and arterial and venous PCO2 in rhesus macaques. Despite its wide margin of safety, ketamine may produce undesired effects. Ketamine increases intracranial pressure and cerebral blood flow and should be used with caution in cases of cerebral trauma or intracranial masses. Poor muscle relaxation, tonic-clonic movements, and psychotomimetic emergence reactions following ketamine administration have been reported. Ptyalism is often noted following administration of the drug.

7.6.2. Ketamine-xylazine

The combination of ketamine and xylazine, an α2-adrenergic agonist, produces sufficient muscle relaxation and analgesia for minor surgical procedures. Ketamine (7 mg/kg IM) and xylazine (0.6 mg/kg IM) provided adequate anesthesia for cisternal or lumbar puncture, digit amputations, and urinary catheterization in rhesus macaques. Heart rate, respiratory rate, and body temperature were more depressed than with ketamine alone. Ketamine-xylazine and xylazine alone produced significant decreases in mean arterial pressure and heart rate compared with ketamine alone in rhesus macaques.

7.6.3. Ketamine-diazepam

The combination of ketamine (5-10 mg/kg) and diazepam (0.2-0.4 mg/kg) produces reliable sedation in Old World species. A higher dose of diazepam (1 mg/kg) is used in marmosets and squirrel monkeys. However, intramuscular administration of diazepam can be painful and absorption unreliable with multiple doses prolonging recovery (Popilskis and Kohn, 1997). It should be noted that diazepam does not provide any analgesia.

7.6.4. Ketamine-midazolam

Midazolam is better absorbed after intramuscular administration than diazepam and results in more predictable sedation. It has a shorter elimination half-life and can be used as an infusion. Midazolam (0.05-0.15 mg IV, repeated as needed) combined with ketamine (15 mg/kg then 12/mg/kg/hr infusion) has been used for PET imaging in rhesus macaques and vervets. Midazolam effects may differ with age in vervets with younger animals requiring a higher dose.

7.6.5. Ketamine-medetomidine

Medetomidine, an α2-adrenergic agonist, when used in combination with ketamine provides anesthesia sufficient for minor procedures. Ketamine-medetomidine is a combination that is widely used in the UK. Medetomidine alone produces a significant decrease in mean arterial pressure, an increase followed by a decrease in respiratory rate, bradycardia, hypotension, arrhythmias, and hypothermia in rhesus macaques; intramuscular administration may blunt the cardiovascular effects of medetomidine. Ketamine (4 mg/kg) and medetomidine (150 µg/kg) produced complete immobilization with good muscle relaxation in wild red howler monkeys. Reversal with atipamezole resulted in smooth and rapid recovery making this a good anesthetic agent for field work. Medetomidine (50-100µg/kg) in combination with ketamine has been used in rhesus macaques. The combination of ketamine and medetomidine produces a deeper, more level plane of anesthesia in macaques than ketamine alone; duration of effect is longer. It should be noted that the use of medetomidine alone is not recommended as it produces inconsistent sedation in many species, and animals can be readily roused.

7.6.6. Tiletamine/zolazepam

Tiletamine/zolazepam (Telazol) is a combination of the dissociative anesthetic tiletamine and the benzodiazepine tranquilizer zolazepam. Like ketamine, tiletamine/zolazepam has a wide margin of safety in nonhuman primates, but tiletamine/zolazepam produces more muscle relaxation than ketamine and a longer duration of anesthesia. Onset of effect is rapid, and recovery is smooth. Tiletamine/zolazepam (4-6 mg/kg IM) is useful for minor procedures in macaques; the duration of effect lasts approximately 45-60 minutes in macaques and is dose-dependent. Tiletamine/zolazepam can be used for chemical restraint and minor procedures in small primates such as marmosets, tamarins, squirrel monkey, and capuchins. New World primates require a higher dose; a dose of 10 mg/kg has been used in squirrel monkeys.

7.6.7. Propofol

Propofol may be used as an induction agent following chemical restraint with ketamine to allow relaxation prior to insertion of an endotracheal tube. It may also be given as a sole anesthetic agent by constant rate infusion. Benefits of propofol include its quick onset of action and short duration. It is ideal when rapid recovery is required but provides little or no analgesia in the postoperative period. For induction, propofol is given intravenously as a bolus. Subeffective doses may produce excitement, while overdosing commonly results in apnea. If apnea occurs, respiratory support may be provided for 2-3 minutes until redistribution occurs and the anesthetic level lightens. Preparations of propofol may support bacterial growth if vials become inadvertently contaminated. Care should be exercised when adding diluent and vials should be discarded after each use. Propofol is used at a dose of 2-5 mg/kg for Old World primates and 2-6 mg/kg for New World primates. In general 25-50% of the calculated dose is administered as a bolus and titrated until an adequate anesthetic plane is achieved. Since apnea is common during induction with propofol, equipment necessary for respiratory support should be readily available. Repeated boluses can be administered without causing prolonged recovery. Recovery from propofol anesthesia is rapid.Propofol (2-5 mg/kg IV) provides anesthesia with good muscle relaxation sufficient for minor procedures in Macaca mulatta, M. fascicularis, and Papio spp. Propofol (2.5 mg/kg IV, repeated as needed) provided adequate anesthesia for laparoscopy with good muscle relaxation in Macaca fascicularis. Minimal effects on the cardiovascular and respiratory systems were observed; however, doses exceeding 2.5 mg/kg produced apnea. Moderate surgical anesthesia lasting 20-40 minutes was produced by a dose of 10mg/kg. Propofol has been used in Papio spp. as an infusion (0.4-0.6 mg/kg/min following induction with 2.5-3 mg/kg IV) to provide anesthesia for magnetic resonance imaging (MRI). In our experience, induction with propofol (2.5 mg/kg IV) following ketamine (10 mg/kg IM) administration and maintenance with a constant rate infusion of propofol (0.3 - 0.4 mg/kg/min) provides reliable anesthesia for MRI and minor procedures in rhesus macaques.

7.7. Inhalant Anesthetics

Inhalant anesthetics are commonly used in nonhuman primates and have a number of advantages including patient safety and rapid recovery. Anesthesia commonly begins with ketamine administration to provide chemical restraint. Thiopental or propofol can be used as induction agents to facilitate intubation prior to inhalant anesthesia.Technically inhalant anesthetics are more demanding then injectable anesthetics, requiring mastery of additional techniques and the availability of anesthetic equipment. Because use of inhalants is highly dependent on these devices, an appropriate preventative maintenance program should be in place, and a thorough anesthetic checkout list developed and performed prior to each procedure. While masks or chambers may be used for initial induction, tracheal intubation should be used for anesthetic delivery, and selection of breathing systems and bags should be based on standard criteria. Laryngeal spasm may be particularly problematic during intubation of nonhuman primate species. Lidocaine gel may be placed on a cotton-tipped applicator to wipe the larynx gently, and the gel should also be used to lubricate the endotracheal tube. The cheek pouches of Old World species should be checked to ensure that they are empty. The animal should be positioned supine while an assistant holds the upper jaw and pulls the tongue with a gauze sponge. An oral dental speculum may be useful to prevent the jaw from closing. The anesthetist then uses a laryngoscope to depress the tongue gently, visualize the larynx, and guide the endotracheal tube into the trachea. Actual correct insertion of the tube should be confirmed visually. The tube should then be tied with gauze or tape behind the animals head to prevent it from dislodging and the cuff of the tube inflated. Leaking cuffs are a common problem, and the integrity should be checked prior to insertion.Intubation often will induce a cough reflex with the risk of aerosolization of infectious agents resident within the animal’s oropharynx and respiratory tree. Based on risk assessment of the animal and experimental protocol, additional personal protective equipment may be required to provide adequate biosafety to the anesthetist. This may include used of an N95 respirator, face shield, goggles, or powered air purifying respirator.

7.7.1. Isoflurane

Isoflurane is the inhalant anesthetic of choice in nonhuman primates and provides significant advantages over halothane. Isoflurane causes less cardiovascular depression than halothane and does not sensitize the heart to the dysrhyhmogenic effects of catecholamines. Cardiac output is minimally depressed, and cardiac rhythm is stable. Isoflurane does result in dose-dependent hypotension due to reduction in systemic vascular resistance. Hypotension can be pronounced if levels of 3-4% are used with mask induction or if maintenance levels exceed 2%. Isoflurane is minimally metabolized and can be used in primates with liver or kidney disease. MAC of isoflurane is 1.46% in rhesus macaques and 1.28% in cynomolgus macaques. Maintenance of nonhuman primates at 1.3 MAC provides adequate anesthesia for most procedures. Fentanyl can be used with isoflurane (0.5-0.75%) for situations in which minimal cardiovascular depression is required. Isoflurane causes reduction in cerebral blood flow, but cerebral oxygenation remains adequate.

7.8. Intraoperative monitoring and support

7.8.1. Monitoring

A variety of monitoring devices are available to assist in the assessment and maintenance of adequate anesthesia. For minor procedures requiring injectable anesthetics such as ketamine or tiletamine/zolazepam, these may offer little advantage over monitoring pulse, respiratory rate and character and perfusion. For more complicated and prolonged procedures, they offer significantly more information and should be routinely used. Pulse oximetry, EKG, and body temperature are all now easily recorded by noninvasive means. Respiratory rate, mean arterial pressure, blood gases, and expired anesthetic gases provide additional information but require more expensive equipment. They should be available for more difficult or complex cases. While useful, malfunction of monitoring equipment may occur, and these devices should not replace direct visual and physical evaluation of the patient by a well-trained anesthetist.

7.8.2. Depth of anesthesia

A number of physical and physiologic parameters may be measured to assess depth of anesthesia. Physical findings that may be followed by the anesthetist include muscle relaxation, jaw tone, palpebral reflex, swallow reflex, heart rate and sounds, respiratory rate and character, withdrawal reflex, pulse rate and quality, mucous membrane color, and capillary refill time. Additional physiologic parameters including EKG, SpO2, tidal volume, blood pressure, expired anesthetic gases, and body temperature may be measured using different monitoring devices. No single parameter in isolation can accurately reflect anesthetic depth, and experience on the part of the anesthetist is required to interpret these findings properly.Ocular signs used to monitor anesthetic depth tend to be variable in nonhuman primates and influenced by commonly used injectable anesthetics. With ketamine and tiletamine, pupils are dilated and pupillary light reflex and corneal reflex are lost. During stage III (surgical anesthesia), pupils are generally constricted and not responsive to light, the palpebral reflex is sluggish/absent, and the globe is rotated downward. Dilated pupils unresponsive to light are seen in late stage III. Reflexes return, and the globe rotates upward as the level of anesthesia is decreased. It should be kept in mind that dissociative anesthetics such as ketamine can interfere with the interpretation of some of these reflexes.

7.8.3. Intraoperative support

Intraoperative support and intervention may be critical in producing a safe and effective anesthetic experience. Due to the small size of some nonhuman primates and the common use of drugs like ketamine and tiletamine/zolazepam during induction, hypothermia may be problematic. Use of supplemental heat is required during procedures lasting more then 30-45 minutes and in sick or debilitated animals. Commonly used devices include the Bair Hugger air (Arizant Healthcare) and the Gaymar T/pump water blankets (Paragon Medical). Body temperature should be monitored to prevent hyperthermia. Electric blankets or heating pads should never be used due to the risk of thermal burns.

Fluid therapy is also important in order to maintain blood pressure and ensure quick venous access in the event of an emergency. An indwelling catheter may be placed in the saphenous or cephalic vein and lactated Ringer’s solution administered intravenously at a rate of 20 ml/kg for the first hour and 10 ml/kg per hour thereafter. If blood transfusion is anticipated, normal saline is preferred to prevent potential incompatibility with the anticoagulant. An intravenous pump is useful to prevent over-administration of fluids.

Catheter 1
Catheter 1

Catheter 2
Catheter 2

Catheter 3
Catheter 3

Alternate site
Alternate site

Table 4: Some commonly used anesthetics and analgesics

AGENT

DOSAGE

COMMENTS

Acepromazine

0.5-1.0 mg/kg PO, SC, IM

Preanesthetic, tranquilizer

Buprenorphine

0.01 mg/kg IM, IV q12h

0.1-0.3 mg/kg IM q6-12h

Analgesia

Opioid agonist-antagonist

Butorphenol

0.1-0.2 mg/kg IM q12-48h

Analgesia

Diazepam

0.5-1.0 mg/kg PO

0.25-0.5 mg/kg IM, IV

0.1-0.5 mg/kg IM

Sedation

Seizures, muscle relaxation

Lemurs-prevent ket. Induced seizures

Flunixin meglumine

0.3-1.0 mg/kg SC, IV q12-24h

2-4 mg/kg SC SID

Analgesia

Ketamine

5 mg/kg IM

10-15 mg/kg IM

20 mg/kg IM

Great ape/follow w/inhalant anes.

Medium sized primates (10-30kg)

Marmosets/tamarins

Ketamine(K)/

Acepromazine (A)

(K) 4mg/kg/

(A) 0.04mg/kg IM

Lemurs

Ketamine/

Diazepam

(K) 15mg/kg/

(D) 1mg/kg IM

Anesthesia

Ketamine/Xylazine

(K) 10mg/kg/

(X) 0.5mg/kg IM

Anesthesia

Medetomidine(M)/

Ketamine (K)

(M) 40ug/kg/

(K) 2mg/kg IM

Anesthesia

Medetomidine(M)/

Telazol (T)

(M) 0.02-0.06mg/kg/

(T) 0.8-2.3mg/kg IM

Anesthesia

Midazolam

0.1-0.5 mg/kg IM

Pre-anesthetic / lemurs

Morphine sulphate

1-2 mg/kg SC, IM q4h

Analgesic

Naloxone

0.01-0.05 mg/kg IM, IV

Narcotic reversal

Tiletamine/zolazepam (Telazol)

1-20 mg/kg IM

2-6 mg/kg IM

4-10 mg/kg IM

Wide ranges for different species variation

7.8.4. Post operative recovery and analgesics

7.8.4.1. Postoperative recovery

The immediate postoperative recovery period can be a critical time with risk of continued hypothermia, arrhythmias, and aspiration. Direct observation by a trained anesthetist is important for prompt intervention during this time. Once recovery from the anesthetic drugs has occurred, monitoring should continue by trained veterinary and animal care personnel to assess for possible procedural complications, postoperative pain, and residual drug effects.

7.8.4.2. Recovery from anesthesia

Animals should be monitored continuously and directly for body temperature, SpO2, heart rate, and respiratory rate until return of the swallow/gag reflex. The tube may be removed and the oropharynx suctioned or wiped with gauze to remove excess secretions. At this point animals are returned to a recovery or home cage and monitored until able to sit or stand. If telemetry is available, a variety of parameters may be assessed. If not, indirect monitoring of respiratory rate and level of consciousness should continue. Once animals have recovered enough to stand or sit, monitoring may be discontinuous with the patient checked at regular intervals or observed by closed circuit videography. Care must be taken to prevent injury if the animal is returned to an enclosure with other primates. During this time supplemental heat may be required to prevent or correct hypothermia.

7.8.4.3. Assessment of pain

Provision of adequate analgesia is paramount during and following any procedure that may cause more than momentary pain. Since nonhuman primates may not always show signs of pain, preemptive analgesia and use of analgesics following any potentially painful procedure should be the rule. Signs of pain in nonhuman primates may be nonspecific and include anorexia, lethargy, and weight loss. This may be particularly common in chronic pain conditions such as endometriosis or osteoarthritis. Potential clinical signs of pain in nonhuman primates are presented in table below. Staff should be trained to recognize signs of pain in nonhuman primates and protocols developed to change pain medication or adjust the dose, frequency and duration of drug administration to provide adequate analgesia.

7.8.5. Analgesia

As in other laboratory animal species, postsurgical analgesia must be provided to alleviate pain and distress. Often nonhuman primates do not show clinical signs of pain, and use of analgesics should be integrated with anesthetic design. Use of preemptive analgesia to coincide with induction or prior to surgical manipulation has been shown to significantly reduce postoperative pain and improve recovery. Furthermore, postoperative variables in drug absorption such as those caused by hypotension and changes in blood flow may be avoided by administering analgesics prior to surgery. Use of analgesics should be detailed through the course of animal protocol development. In most instances analgesics should be required for 24 hours after a minor surgical procedure and 48 hours after a major surgical procedure. This period may be lengthened based on the type of procedure to be performed and the postoperative monitoring schedule.

7.8.5.1. NSAIDS

NSAIDS may be used in the management of postoperative pain. Benefits include the lack of sedation or respiratory suppression observed with narcotic analgesics. Both ketorolac and carprofen have been used and provide moderate levels of pain relief. NSAIDS inhibit platelet function for prolonged periods; caution is advised if additional surgeries are anticipated or if there is a significant risk of postoperative hemorrhage.

7.8.5.2. Aspirin

Aspirin has analgesic, antipyretic, and anti-inflammatory properties and can be used in nonhuman primates to relieve mild, low-intensity pain. Old World primates can be given 20 mg/kg PO q6-8 hours. Aspirin therapy is not appropriate as a primary analgesic for most postsurgical pain, but may be used in combination with or following opioid analgesia. A pediatric rectal suppository (125 mg for 5 kg primate) can be administered at the conclusion of minor procedures.

7.8.5.3. Ketorolac

Ketorolac is an injectable NSAID that has been used to control moderate postoperative pain. The dose for macaques and baboons is 15-30 mg im. Ketorolac has not been associated with respiratory depression or sedation. It should be noted that ketorolac inhibits platelet function for extended periods and is contraindicated in primates with coagulopathies.

7.8.5.4. Opioids

Opioids have been a mainstay in the postoperative management of pain. While morphine provides good analgesia, the half-life in nonhuman primates is short, and morphine can be associated with significant sedation and respiratory suppression. Newer opioids lack signficant sedation and have longer half-lives, allowing administration on more easily managed intervals. Newer drugs may have complex agonist and antagonist actions that may impact later experimental work. Although technically more difficult, side effects may be minimized when opioids are administered by the epidural route. Finally, new delivery vehicles such as liposome-based depofoam technology (SkyePharma, Inc.) have recently been developed and licensed which may prolong the half-life of these commonly used drugs.

Naloxone (0.01-0.05 mg/kg IV, IM) can be used to reverse the actions of opiate agonists. The dose may need to be repeated to prevent the return of respiratory depression as naloxone is a short-acting antagonist.

7.8.5.5. Morphine

Morphine is an opiate agonist with a wide margin of safety in nonhuman primates. Morphine is used at a dose of 1-2 mg/kg IM or SC q4h to provide postoperative analgesia. Morphine reduces the MAC for isoflurane and causes respiratory depression in rhesus monkeys. A small decrease in arterial pressure was reported in conscious rhesus monkeys. Modest respiratory depression following morphine administration was observed in pig-tailed macaque infants. Hypercarbia was not correlated to declining serum or CSF levels of morphine. Mild respiratory effects and small increase in PaCO2 suggest safe use in macaque infants (Lynn, et al., 1991). A disadvantage of morphine is the short half- life requiring frequent dosing to ensure adequate analgesia. As a result, morphine is not commonly used in nonhuman primates and has been replaced by a number of other agents.

7.8.5.6. Buprenorphine

Buprenorphine is an opioid agonist-antagonist with a longer duration of action that butorphanol. Buprenorphine (0.005-0.01 mg/kg q6-12 hours) has been widely used in many nonhuman primate species for preemptive and postoperative analgesia without excessive sedation or respiratory depression. Buprenorphine has limited respiratory depressant effects in nonhuman primates.

7.8.5.7. Fentanyl

Fentanyl is an opioid agonist that can be administered intraoperatively to reduce the requirement for inhalant anesthesia and to provide analgesia. Fentanyl has been used in macaques and baboons (5-10µg/kg bolus or 10-50 µg/kg/hr infusion) in combination with low concentrations of isoflurane (0.4-1.25%) with minimal cardiovascular effects Respiratory depression is observed with fentanyl. Small doses (2 µg/kg and 4 µg/kg) decreased respiratory rate and increased PCO2 in macaques, and higher doses (64 µg/kg) produced decreases in mean arterial pressure and cardiac output and apnea. Transient decreases in heart rate and mean arterial pressure were observed after fentanyl administration in rhesus monkeys anesthetized with isoflurane.

Clinical signs of pain in NHPs

Clinical sign

Comment

Anorexia

These may represent common and nonspecific signs of pain

Lethargy/reluctance to move

Decreased grooming

Withdrawal from cage mates

Weight loss

Tachypnea

Can be associated with acute pain; many other causes including acidosis, cardiovascular collapse and serious pulmonary dysfunction

Bruxism

These can be associated with oral, esophageal or gastric pain; less commonly associated with pain at other sites; may be caused by GI dysfunction with no pain.

Ptyalism

Vomiting

Abdominal splinting

Can be difficult to observe; causes would include peritonitis, abdominal surgery

Rubbing, licking or biting at site

Suggestive of localized pain

Lameness

Stiff gait

Inflammation

Pain is a cardinal sign of inflammation and includes swelling, redness and possible discharge.

Head pressing/head tilt

Possible sign of CNS pain

8. References and Resources

Conservation Medicine Challenges 1, 2, 3

Supplemental Readings

Sources of information about primate medicine are available in many forms, including books, journals, the Internet and personnel communications. The following is an abbreviated list of some resources taken from the Primate Info Net on helpful resources for a primate veterinarian working collection.

8.1. Professional Organizations

Association of Primate Veterinarians http://www.primatevets.org/

American Association of Zoo http://www.aazv.org/

8.2. Websites

The Internet offers a wide range of topics on primates. One must understand, however, that there is no peer review system of the Internet and therefore, caution must be used when using the Internet as a source of information. That said, it is an excellent resource for contacting primate experts concerning a wide range of issues. One of the most helpful sites for primate information is the PRIMATE INFO NET, a site operated by the Wisconsin Regional Primate Research Center, University of Wisconsin -Madison.

This web site is http://pin.primate.wisc.edu/

CDC www.cdc.gov

Chimp Haven, a federal government supported permanent home for chimpanzees retired from the biomedical research community, entertainment industry, or kept as pets. http://www.chimphaven.org/

Primate listserv http://groups.yahoo.com/group/alloprimate/

Anesthesia and Analgesia of Laboratory Animals http://research.uiowa.edu/animal/?get=aa_regimens

Code of Federal Regulations (CFR) http://www.gpoaccess.gov/cfr/about.html

8.3. Books

Ankell-Simons, Friderun and Fleagle, John G. Primate Anatomy: An Introduction, 2nd ed. Academic Press, 2000.

Bennett, B. Taylor, Christian R. Abee, and Roy Hendrickson, eds. Nonhuman primates in biomedical research, vol. 1: Biology and management, vol. 2: Diseases. San Diego: Academic Press, 1995-1998, 2 vols. ISBN 0120886618 (v.1) and 0120886650 (v.2).

Berringer, Orville M., Jr., Freddie M. Browning, and Charles R. Schroeder. An atlas and dissection manual of rhesus monkey anatomy. Tallahassee, Fla.: Anatomy Laboratory Aids, 1968.

Biology and Medicine of Non-human Primates, Part 1 & 2 IN: Laboratory Animal Medicine and Management, Reuter J.D. and Suckow M.A. (Eds.). International Veterinary Information Service, Ithaca NY (www.ivis.org)

Colley, Rob, ed. Marmosets and tamarins in captivity. Bristol: The British Association of Wild Animal Keepers, 1993.

Committee on Well-Being of Nonhuman Primates, Institute for Laboratory Animal Research, Commission on Life Sciences, National Research Council. The psychological well being of nonhuman primates. Washington, DC: National Academy Press, 1998. ISBN 0309052335.

Flecknell, P.A. Laboratory animal anaesthesia: a practical introduction for research workers and technicians, 2nd ed. Academic Press, 1996. ISBN 0122603613.

Fowler, Murray E. and Miller, R. Eric. Zoo and Wild Animal Medicine, 5th ed. Saunders, 2003. Chapters: 37-39.

Fox, JG, Cohen, BJ, Loew, FM. Laboratory Animal Medicine. Orlando, Florida: Academic Press; 1984

Hawk, C. Terrance and Steven L. Leary, comp. Formulary for laboratory animals. Ames, Iowa: Iowa State University Press, 1995. ISBN 0813824222.

Hrapkiewicz, Karen, Laticia Medina and Donald D. Holmes. Clinical medicine of small mammals & primates: an introduction, 2nd ed. London: Manson, 1998. ISBN 1874545952.

Johnson, David K., Robert J. Russell and Jim A. Stunkard. A guide to diagnosis, treatment and husbandry of nonhuman primates. Edwardsville, Kan.: Veterinary Medicine Pub. 1981.

Kirkwood, James K. and Katherine Stathatos. Biology, rearing, and care of young primates. Oxford University Press, 1992. ISBN 0198547331.

Physician's Desk Reference. Medical Economic Co. 1998; 2494

Scott, GBD. Comparative Primate Pathology, 1992. ISBN 0198576404.

8.4. Articles

Bielli M., Lauzi S., Pratelli A., Martini M., Dall'Ara P., Bonizzi L. Pseudotuberculosis in Marmosets, Tamarins, and Goeldi's Monkeys (Callithrichidae / Callimiconidae) Housed at a European Zoo. Journal of Zoo and Wildlife Medicine 30(4): 532-536, 1999.

Brooks, P. Are You Sure You Want A Monkey? Brochure- The Simian Society of America, Inc.

Carpenter JW. Mashima TY. Rupiper DJ. Exotic Animal Formulary. Greystone Publications. 1996; 272-274

Cogswell, F. B. Malaria and Piroplasms of Non-Human Primates, IN: Companion and Exotic Animal Parasitology, Bowman D.D. (Ed.) IVIS Website .

Ellenberger, U. Factors influcencing the parasite status of gorilla subspecies (Gorilla beringei graueri, Borilla beringei beringei, Gorilla gorilla gorilla): a plea for a multidisciplinary approach in conservation medicine. Proceedings of the AAZB and IAAAM Joint Conference, 2000: 160-165.

Fahlman A. Bosi EJ. Nyman GN. Immobilization of Southeast Asian Primates with Medetomidine, Zolazepam and Tiletamine, and Reversal with Atipamezole. Proc. American Assoc of Zoo Veterinarians 1999: 334.

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