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Standard Operating Procedures for Working
with Laboratory Primates
Harvard Medical Area
Center for Animal Resources and Comparative
Medicine
Contents:
Zoonoses ........................................................................................................................................................... 2
Prevention of exposure .................................................................................................................................. 2
Animal handling ............................................................................................................................................. 2
Review of zoonotic diseases of nonhuman primates .................................................................................... 3
Blood borne parasites .................................................................................................................................... 4
Tuberculosis .................................................................................................................................................. 4
Herpes B (Herpesvirus simiae) ...................................................................................................................... 5
Need more information? ................................................................................................................................ 6
Protective equipment and safety practices ....................................................................................................... 6
Purpose ......................................................................................................................................................... 6
General Information ....................................................................................................................................... 6
Compliance .................................................................................................................................................... 7
Responsible Persons and Enforcement ........................................................................................................ 7
Work clothing and work shoes ....................................................................................................................... 7
Personal protective equipment ...................................................................................................................... 7
Personal Hygiene .......................................................................................................................................... 8
Training .......................................................................................................................................................... 8
Post exposure management of macaque bites and scratches ......................................................................... 8
Examination and culturing of nonhuman primate .......................................................................................... 9
Injuries on nights and weekends ................................................................................................................. 10
Postexposure monitoring ............................................................................................................................. 10
Directory for Medical Care of Monkey Bites and Scratches............................................................................ 10
Harvard Medical Area (Monday – Friday, 9 AM – 4 PM)............................................................................. 10
Brigham and Women’s Hospital Occupational Heath Services (Monday – Friday, 7:30 AM – 4:30 PM) ... 10
Nights, Weekends, Holidays ........................................................................................................................ 10
Infectious Disease Consultant ..................................................................................................................... 11
ARCM Veterinary Staff ................................................................................................................................ 11
NIH B Virus Resource Laboratory ............................................................................................................... 11
References ...................................................................................................................................................... 11
What to do if you are injured ........................................................................................................................... 11
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Zoonoses
Zoonoses are diseases which humans contract from animals. Monkeys pose a
particular hazard to animal care workers because bites, scratches and contact
with feces occur frequently during routine husbandry procedures and because
humans and monkeys are susceptible to many of the same pathogens. Some
primate zoonoses cause treatable but potentially debilitating illness (e.g.
Shigella, campylobacter diarrhea) while others may be fatal (e.g. Herpes B
infection). Monkeys are also susceptible to many human diseases.
Devastating losses have occurred when infected humans transmit tuberculosis
and measles to captive primates. These notes will discuss general principles
that animal care workers should follow to avoid infection. Clinical features of
the common zoonoses and the diseases that people can transmit to monkeys
will be discussed.
Prevention of exposure
Personal hygiene and work practices
Bacteria and viruses may be eaten, inhaled or injected by animal bites or
contaminated needles. Intact skin is a good barrier against infection. Most
bacteria and viruses are killed by soap and water.
Wear appropriate protective clothing. Use disposable gloves and masks when
handling monkeys or changing cages. Do not bring work clothes or shoes
home. Change soiled clothing promptly.
Don’t use needles and syringes unless you have been trained. Dispose of used
needles promptly and safely. Do not recap needles. Be familiar with any
special protocols regarding needle handling that have been developed for your
area.
Observe personal hygiene. Wash hands carefully and frequently. Remove
laboratory jackets before eating.
Take care of injuries promptly. Report to the nurse or supervisor as soon as
possible after an injury.
Be aware of clinical signs of illness in yourself. Report illness to the nurse or
your supervisor. This is important for your own protection, for the health of
your coworkers, and for the health of the monkeys
Animal handling
Follow appropriate monkey handling techniques.
Use chemical restraint for any invasive procedure.
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Do not handle monkeys unless you have been appropriately trained. Learn to
anticipate monkey behavior; learn the behavior of individual monkeys that you
work with. Ask for help from the animal’s regular attendant.
Learn the behavior patterns of monkeys in your area. Be calm when working
around monkeys. Avoid shouts, direct stares and other provocative gestures
that might antagonize them. Be vigilant around monkeys. Never enter a
group cage of monkeys unless you have been properly trained and have the
proper equipment. Anticipate aggressive behavior by monkeys.
Use extra caution when capturing or examining conscious monkeys. Use
heavy leather gloves or nets for protection against bites and scratches when
hand-catching conscious monkeys.
Be aware of clinical signs of illness in monkeys and notify clinical veterinarians
about sick animals. Observe posted warnings and signs.
Review of zoonotic diseases of nonhuman primates
Gastrointestinal zoonoses
Monkeys may harbor bacteria that cause debilitating diarrhea in people. Most
infected animals are acutely ill and very weak. Monkeys may also shed large
numbers of bacteria in their feces without serious illness. People may also
shed these bacteria asymptomatically. Diagnosis of all of these infections is
by culture of the feces.
Campylobacteriosis
Campylobacter jejuni is common in all species of nonhuman primates.
Asymptomatic shedding is common. Food and water are also common sources
of campylobacter infections.
The clinical signs of campylobacter in monkeys are variable. Some monkeys
will have mild diarrhea that resolves without treatment. Other monkeys will
have severe diarrhea that causes weight loss and dehydration. Blood and
mucous may be seen in feces.
Treatment involves supportive care (oral electrolytes) and antibiotics
(erythromycin). Mild cases may resolve without antibiotics.
The disease in people is similar to that in monkeys. Severe diarrhea with
abdominal cramps may occur.
Shigellosis
Shigella flexneri is a common cause of diarrhea in macaque monkeys.
Although S. sonnei is the most common cause of shigellosis in man, cross
infection is possible. Humans may also be the reservoir for monkey infections,
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but asymptomatic carriers may maintain the infection in the colony between
outbreaks. Shigella is very infectious and as few as 500 bacteria will causes
infection. Children are more susceptible than adults. Outbreaks are more
common in hot weather.
Diarrhea with blood and mucous is the most common clinical sign. Shigellosis
may be fatal in monkeys if untreated, but most animals respond rapidly to
antibiotics and parenteral fluids.
Affected monkeys should be isolated.
The human disease is often mild in adults, but may be very debilitating or fatal
in children.
Other enteric bacteria and parasites
Yersinia enterocolitica is more rare than the previously mentioned pathogens,
but can also cause severe diarrhea and dehydration in people and monkeys.
Salmonella is not common in nonhuman primates. Infection can occur from
contact with an infected person or from consumption of contaminated food,
especially poultry. Mild or severe diarrhea can occur. Escherichia coli
occasionally causes diarrhea which may either watery or contain blood and
mucous. Giardia lamblia, Cryptosporidium parvum, Enterocytozoan bieneusi,
Balantridium coli, and Entameba histolytica are all intestinal protozoa that can
infect monkeys and man. Diarrhea can range from mild to severe. These
parasites are rare in most laboratory primates. Wild-caught monkeys
occasionally harbor other parasites that can infect people.
Blood borne parasites
Wild-caught monkeys may carry several parasites in their blood. The animals
may have very minor clinical signs. Casual contact or routine handling is safe,
but needle stick injuries may be hazardous. Trypanosoma cruzi is a blood
borne protozoan that causes Chagas’ disease. Chagas’ disease causes
debilitation and cardiomyopathy in man. Many wild-caught squirrel monkeys
carry this parasite. Malaria (Plasmodium spp) may also be present in wild
caught monkeys.
Tuberculosis
Tuberculosis is a serious concern at all laboratory primate facilities.
Tuberculosis is rare in wild monkeys but can readily be acquired from infected
humans. All species can be affected. Our colony has been free of
Mycobacterium tuberculosis for greater than 15 years but we remain vigilant
due to the severity of disease following transmission of the bacteria from
humans to animals. Tuberculosis causes severe weight loss, lethargy and
coughing and is almost always fatal in monkeys, but the disease can go
unrecognized for months during which time other animals may be infected.
Strict quarantine of new animals and regular testing of the entire colony
identifies asymptomatic monkeys. Infected animals are not treated.
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People may have asymptomatic infections or may suffer severe respiratory
disease and weight loss. Routine tuberculin testing detects most human
cases. All individuals who work with monkeys, including visiting faculty and
students, must have annual skin tests to show that they do not have
tuberculosis. Individuals with positive skin tests must have an alternate
evaluation such as a chest radiograph by a health professional before they
may work with primates. Harvard Medical School staff and students may
obtain tuberculin skin tests or radiographs at no charge from the University
Health Services (432-1370). Individuals with other primary affiliations should
be tested at their home institution. Written documentation of tuberculin skin
test results must be presented to the ARCM Associate Director for Operations
(Dr. D. Lee-Parritz) before requesting access to nonhuman primate facilities.
Herpes B (Herpesvirus simiae)
Herpes B virus infection of man is very rare but is often fatal. The Herpes B
virus is present in about 25% of rhesus and cynomolgus monkeys; only 2-3%
of these monkeys have clinical signs at a given time. Herpes B virus does not
infect baboons, squirrel monkeys or owl monkeys. Infected animals may have
conjunctivitis or ulcers or white plaques on the lips, nares, tongue, palate or
genitalia. Diagnosis of Herpes B infection in monkeys is often difficult because
infected animals may not have detectable antibody and shed virus only
intermittently. For that reason, you must assume that all macaque monkeys
are potential carriers of this virus.
Infection of man may occur after bites, scratches, needle sticks, splashes to
the eye or injuries caused by macaque caging. The incubation period of the
disease in man is between 2 weeks and 6 months. Pain, numbness and
weakness of the affected arm may occur, accompanied by generalized malaise
and flu-like symptoms. Coma and death result from central nervous system
infection. Due to the severe consequence of human B virus infection, all
injuries caused by macaques or their caging must be taken seriously. In the
event of an injury washing the wound for 15 minutes is the most important
first step. The injured employee must report the injury to the supervisor and
occupational health services for evaluation.
Other viruses
Herpes viruses are common in other primate species but are not hazardous to
humans. In general, these viruses do not cause disease in their natural hosts
but can be fatal to other primate species. In particular, Herpesvirus saimiri
and Herpesvirus tamarinus cause no clinical disease in squirrel monkeys but
are lethal in owl monkeys and marmosets. Human herpes viruses are highly
pathogenic for owl monkeys and marmosets. Animal care workers should take
care to avoid cross contamination of these species by the use of shared
equipment and should not work with New World species when they have active
cold sore lesions.
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Measles
Measles is rare in wild monkeys but unvaccinated monkeys acquire the disease
readily from other monkeys or from infected people. Unvaccinated or
improperly vaccinated people may contract the disease from monkeys during
an outbreak. Improperly vaccinated people may introduce the infection into a
primate colony. The incubation period in monkeys is usually 5-15 days.
Affected animals develop conjunctivitis, lethargy, and a diffuse rash.
Pneumonia, abortion, secondary bacterial infection and death can occur. New
World monkeys are more susceptible to measles than are Old World monkeys.
Our monkeys are protected by vaccination but we remain vigilant due to the
severity of disease following transmission of the virus from humans to
animals.
Immunodeficiency viruses.
Infection of monkeys with Simian Immunodeficiency Virus (SIV) causes an
AIDS-like syndrome in macaques but only occurs in experimental infectious
disease laboratories. There are no macaques infected with SIV at the
Longwood campus. SIV is not known to be pathogenic to people, but it is
closely related to human immunodeficiency virus (HIV) and the virus can
infect human cells in tissue culture. Type D retrovirus is another
immunosuppressive macaque retrovirus that can cause diarrhea, weight loss
and recurrent infections. Macaques at the Longwood Medical Area are
regularly screened for this virus to prevent inadvertent introduction of infected
animals. D retrovirus is not infectious to people.
Need more information?
Please ask a member of the veterinary staff to explain any information in this
pamphlet that is not clear to you. You may also speak with an occupational
health professional if you have personal medical questions related to your
work with laboratory animals.
Please contact your supervisor if you require additional training or if adequate
protective equipment is not available to you.
Protective equipment and safety practices
Purpose
The purpose of this section is to describe safe work practices when handling
laboratory primates. They are intended to protect employees working with
macaques or macaque tissues from the risk of Herpes B virus infection and
other infectious diseases.
General Information
Monkeys are wild animals and can cause serious physical injury or infection
through bites, scratches, spitting, and passively by contact with contaminated
fluids or tissues. A summary of known infectious agents that monkeys may
transmit to people is contained in the previous section of this handout.
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Monkeys may also harbor unknown or difficult-to-diagnose pathogens. For
these reasons, you must always use good work practices and use personal
protective equipment when working with nonhuman primates.
Compliance
No one may work with a monkey until he or she has received orientation and
training in the measures described in this manual.
Employees must wear work clothing and personal protective equipment and
follow all work practices and safety measures described in this manual.
Responsible Persons and Enforcement
Procedures described in this manual are the personal responsibility of all
personnel working with monkeys. These include the following employees:
Principal Investigators, Research Technicians, Veterinarians, and Animal Care
Technicians.
Compliance with requirements for personal protective equipment shall be
monitored and enforced by the facility manager, animal care supervisors,
veterinarians and environmental health and safety officer. Noncompliant
ARCM employees are the responsibility of the Associate Director for Animal
Care and the Director of ARCM. Noncompliant research staff are the
responsibility of the Principal Investigator and Department Chair. Individuals
who repeatedly fail to follow required procedures are subject to progressive
disciplinary action, which may include reassignment or termination.
Work clothing and work shoes
The employer will provide all necessary work clothes (scrubs, uniforms or lab
coats) and personal protective equipment (PPE) to personnel working with
monkeys.
Animal care technicians working in animal rooms must wear work clothing and
work shoes at all times. Research staff and veterinarians may wear laboratory
coats over street clothes. Soiled work clothing and laboratory coats must be
placed in suitably labeled hampers for laundering by the laundry service.
Employees must not launder work clothing at home. Work shoes must be kept
in a locker at the Center and should not be worn home.
Personal protective equipment
All staff must use supplementary PPE when working in nonhuman primate
rooms or clinical procedure rooms, or when working with potentially
contaminated cages, bedding, or equipment. Research staff must wear a mask
whenever a nonhuman primate is present in a laboratory, however the use of
eye protection is required only if the investigator is working within 1m (3 feet)
of a nonhuman primate.
Face (“surgical” or “comfort”) masks.
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Eye protection, including brow and side guards. A face shield is required when
washing cages or rooms.
Sleeve protectors are required when feeding, scraping, changing water bottles
or transferring macaques
Gloves
Employees with skin lesions such as dermatitis, abrasions and lacerations
must consult with an occupational health professional before work to evaluate
the potential need for additional personal protective equipment such as bioocclusive dressings or assignment to a different task.
Personal Hygiene
Frequent hand washing is the most important part of good personal hygiene.
Employees must always wash their hands after working in the animal facility,
especially before eating.
It is recommended but not required that all employees working with animals
shower at the end of the workday before changing into street clothing and
street shoes.
Training
Employees will be trained at the time of hire in the following points:
Safe work practices in animal care
Herpes B virus risks and transmission
Risks associated with working with monkeys
Zoonosis training
Standard operating procedures for personal protective equipment; how to put
on, use and take off
Limitations of personal protective equipment
Injury reporting
Continuing education on these points will occur annually and as needed to
ensure employee compliance.
Post exposure management of macaque bites and scratches
Stop what you are doing. If you are working with an animal, secure it in the
cage. Notify your supervisor.
If you were bitten or scratched by a macaque, take precautions against Herpes
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B infection. Supplies and additional information are in the B Virus Bite Kit that
is in each animal room. You must do the following three things immediately:
1.
Disinfect your wound. Wash the wound with the Betadine ®
scrub brush and water for 15 minutes. If there is no Betadine ®
scrub brush, wash with any hand soap or detergent for 15
minutes. For an eye splash, go to closest eye wash station and
rinse the affected eye for 15 minutes or until container is empty.
2.
See an occupational health professional. Call the University
Health Services clinic (432-1370). If you are a Brigham and
Women’s Hospital employee, call BWH Occupational Health (7326034). Tell them that you have been bitten or scratched by a
macaque and that you must be seen immediately. If the UHS or
BWH Occupational Health Clinics are closed, call the Brigham
and Women’s Hospital emergency department (732-5636). Bring
the packet of printed materials in the bite kit with you to the
clinic.
3.
Have the animal evaluated for possible Herpes B infection.
Samples must be collected the same day as the injury. Call the
ARCM main number (432-1285) and ask the veterinary staff to
evaluate the primate, and collect serum and culture samples. On
weekends and holidays, page the on-call veterinarian. The
emergency schedule and contact information is posted in each
animal facility.
If you were bitten or scratched by any other primate, you should disinfect your
wound and see an occupational health professional as described in steps 1 and
2. It is not necessary to evaluate species other than macaques for possible
Herpes B infection.
Examination and culturing of nonhuman primate
As soon as possible following the exposure, the ARCM veterinary staff will
tranquilize and examine the primate. Call the ARCM main number (432-1285)
and ask the veterinary staff to evaluate the primate, and collect serum and
culture samples. On weekends and holidays, page the on-call veterinarian. The
emergency schedule and contact information is posted in each animal facility.
The examination will include observation of the oral cavity, conjunctiva, and
genitalia. If ulcers, vesicles or erosions are present, the veterinarian will
notify the occupational health professional. All exposures from animals with
suspect lesions will be considered “high risk.”
The veterinary staff will collect serum for Herpes B antibody determination as
well as viral cultures from all macaques that bite or scratch. Cultures will be
obtained from the oral cavity, conjunctiva and any suspect lesions. Specimens
for viral culture will be obtained using approved viral transport swabs. Serum
samples and cultures will be sent to the NIH N Virus Resource Laboratory
(University of Georgia, telephone 404-651-0808) for analysis. Cultures must
be shipped overnight express on dry ice and the lab must be called to expect
the shipment. Serum samples may accompany the cultures, or may be sent
separately with “blue ice” packs. A 2 ml serum aliquot will be retained at
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ARCM, frozen at -20oC. The serum antibody check will be repeated two weeks
after the injury.
Injuries on nights and weekends
If an exposure occurs on a weekend or holiday, the Brigham and Women’s
Hospital emergency department will provide emergency care of the employee.
The on-call veterinarian must be called to evaluate and collect samples from
the primate. Cultures may be safely frozen at -20oC for 48 hours prior to
shipment to the Herpes Virus Reference Laboratory. The veterinary call
schedule is posted in each animal area. A directory of veterinary staff office
and pager numbers is also included in this directory.
Postexposure monitoring
Results of the monkey’s B virus culture will be reported to the occupational
health professional who will inform the employee of the results. Should the
culture be positive or indeterminate or if the employee experiences symptoms
of possible B virus infection, the employee will be immediately referred to an
infectious diseases specialist for further treatment. A positive antibody test on
a previously seronegative animal with a negative culture may also require
additional treatment or antiviral drug treatment according to the physician’s
evaluation.
An accident report will be processed with a copy filed with the ARCM Associate
Director for Operations (David Lee-Parritz DVM).
An occupational health professional will monitor the individual weekly for three
weeks after the injury. These visits will be documented in the individual’s
medical record.
If the primate’s culture and antibody test is negative and the employee
remains asymptomatic, no other medical treatment will be necessary.
Directory for Medical Care of Monkey Bites and Scratches
Harvard Medical Area (Monday – Friday, 9 AM – 4 PM)
University Health Services (Peter Massicott, MD) 275 Longwood Avenue,
Boston MA 02115 (617) 432-1370
Brigham and Women’s Hospital Occupational Heath Services (Monday
– Friday, 7:30 AM – 4:30 PM)
(617) 732-6034 or (617) 732-8501
Nights, Weekends, Holidays
Brigham and Women’s Hospital Emergency Room
(617) 732-5636
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Infectious Disease Consultant
R. Paul Johnson, MD.
508/624-8148 (office - NERPRC)
617/726-3812 (office - MGH)
617/726-5772(lab)
617/726-7777 (Beeper 32519)
ARCM Veterinary Staff
David Lee-Parritz DVM (617) 432-2162 (office)
Angie Warner DVM
(617) 432-0888 (office)
(617) 236-9203 (pager)
(617) 236-9196 (pager)
NIH B Virus Resource Laboratory
Viral Immunology Center
Georgia State University
50 Decatur Street
Atlanta, GA 30303
(404) 651-0808
(404) 651-0814 (fax)
http://www.gsu.edu/~wwwvir/index/html
References
1. Bennett B.T., Abee C.R., Henrickson R. Nonhuman Primates in Biomedical
Research: Diseases. Academic Press 1998. pp 1:1-48, 2:59-102, 3:111-179.
2. Brack M. Agents Transmissible from Simians to Man. Springer-Verlag Berlin
Heidelberg 1987.
3. Holmes G.P., Chapman L.E., Stewart J.A., et al. Guidelines for the
Prevention and Treatment of B-Virus Infections in Exposed Persons. In:
Clinical Infectious Diseases 1995; 20:421-39.
What to do if you are injured
Stop what you are doing. If you are working with an animal, secure it in the
cage. Notify your supervisor.
If you were bitten or scratched by a macaque, take precautions against Herpes
B infection. Supplies and additional information are in the B Virus Bite Kit that
is in each animal room. You must do the following three things immediately:
4.
Disinfect your wound. Wash the wound with the Betadine ®
scrub brush and water for 15 minutes. If there is no Betadine ®
scrub brush, wash with any hand soap or detergent for 15
minutes. For an eye splash, go to closest eye wash station and
rinse the affected eye for 15 minutes or until container is empty.
5.
See an occupational health professional. Call the University
Health Services clinic (432-1370). If you are a Brigham and
Women’s Hospital employee, call BWH Occupational Health (7326034). Tell them that you have been bitten or scratched by a
macaque and that you must be seen immediately. If the UHS or
BWH Occupational Health Clinics are closed, call the Brigham
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and Women’s Hospital emergency department (732-5636). Bring
the packet of printed materials in the bite kit with you to the
clinic.
6.
Have the animal evaluated for possible Herpes B infection.
Samples must be collected the same day as the injury. Call the
ARCM main number (432-1285) and ask the veterinary staff to
evaluate the primate, and collect serum and culture samples. On
weekends and holidays, page the on-call veterinarian. The
emergency schedule and contact information is posted in each
animal facility.
If you were bitten or scratched by any other primate, you should disinfect your
wound and see an occupational health professional as described in steps 1 and
2. It is not necessary to evaluate species other than macaques for possible
Herpes B infection.
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