Assessing and Avoiding Risk

Most workers who develop allergic reactions to laboratory animals will do so within the first twelve months of working with them. Infrequently, reactions only occur after working with animals for several years. Initially, the symptoms are present within minutes of the worker’s exposure to the animals. Approximately half of allergic workers will have their initial symptoms subside and then recur three or four hours following the exposure.

If additional respiratory protection is required, the worker should contact the Environmental Health and Safety Department, at (617) 638–8830 on Boston University Medical Campus (BUMC) or (617) 353–4094 on Charles River Campus (CRC). You must also complete an EHS ROHP OSHA Respiratory Medical Evaluation Questionnaire. If you have any known or suspected animal allergies, please complete the Animal Allergy Screening form. Completed forms should be submitted it to the Research Occupational Health Program (ROHP) at 72 E. Concord Street, Evans Building, 8th floor, Room 825.

A 2001 article by D.J. Harrison explores ways to control exposure to laboratory animal allergens.

• Employee protection in the nonhuman primate environment includes the use of protective, and in some cases, waterproof clothing.
• Shoe covers prevent transfer of pathologic organisms. Clothing and shoe covers are specific to the animal spaces but should be removed when outside of those areas.
• Combinations of goggles/masks and/or face shields protect the eyes, nose and mouth from splashes (see details below).
  Gloves are worn to protect contamination of the skin. In the circumstances when awake nonhuman primates will be handled, thick leather gloves specially designed for protecting against bites and scratches should be worn.
• Proper hand washing should be performed before and after wearing the protective clothes.

Bites, scratches, and splashes of blood and body fluids from nonhuman primates pose numerous problems. Bacterial infections are the most frequent complication of a nonhuman primate bite. Cercopithecine Herpesvirus-1 or B Virus is a member of the herpes family occurring naturally in Macaque and possibly other old world monkeys. Most have no evidence of infection or others may have small blisters or ulcerations in the mouth, face, lips, genitalia, and/or eye. Transmission to humans occurs by exposure to contaminated monkey saliva, secretions, or tissues. The most likely route is bites, scratches or splashes. The B Virus has never been cultured in blood. Injuries involving contact with nonhuman primate blood are potentially hazardous. Simian Immunodeficiency Virus (SIV) commonly persists without clinical manifestations in nonhuman primates. Type D Retroviruses (Simian retroviruses [SRV]) may infect some nonhuman primates. However, there is no current evidence of humans being infected with the type D retroviruses.

Description of Common Non-Human Primate Procedures at BUMC and Required Eye/Face Personal

NHP Cage Changing

Eye/Face/Mucous Membrane Protections:

Goggles and surgical mask

Alternative, if available:

Safety glasses, face shield and surgical mask

NHP Dental Cleaning

Eye/Face/Mucous Membrane Protections:

Goggles and surgical mask

Alternative, if available:

n/a

NHP Live AnimalTransport or Removal to Transport Cage

Eye/Face/Mucous Membrane Protections:

Goggles and surgical mask

Alternative, if available:

Safety glasses, face shield and surgical mask

Anesthetized NHP Animal transport

Eye/Face/Mucous Membrane Protections:

Goggles and surgical mask

Alternative, if available:

Safety glasses, face shield and surgical mask

NHP Surgery on Anesthetized Animal using Surgical Microscope

Eye/Face/Mucous Membrane Protections:

Safety Glasses (prescription if needed) with Surgical Loupes, Surgical Mask for Lead Surgeon. All surgical assistants in room should wear goggles and surgical mask .

Alternative, if available:

Lead surgeon currently wearing prescription eyeglasses with side shields and surgical loupes over the glasses with a surgical mask. Alternatively, surgical assistants can wear safety glasses, face shield, and surgical mask.

NHP Surgery on Anesthetized Animal using Surgical Loupes

Eye/Face/Mucous Membrane Protections:

Safety Glasses (prescription if needed) with Surgical Loupes, Surgical Mask for Lead Surgeon. All surgical assistants in room should wear goggles and surgical mask.

Alternative, if available:

Lead surgeon currently wearing prescription eyeglasses with side shields and surgical loupes over the glasses with a surgical mask. Alternatively, surgical assistants can wear safety glasses, face shield, and surgical mask.

Tracheal Tube Insertion and Removal during the beginning and end of NHP Surgery

Eye/Face/Mucous Membrane Protections:

Goggles and surgical mask.

Alternative, if available:

safety glasses (prescription if needed), face shield and surgical mask.

Perfusion of NHP at Termination Surgery

Eye/Face/Mucous Membrane Protections:

Completed in Fume Hood by Lead Surgeon: Involves slicing of heart ventricles, NHP anesthetized.

Alternative, if available:

Completed in Fume Hood by Lead Surgeon: Currently wears prescription eyeglasses and surgical loupes and surgical mask.

Magnetic Resonance Imaging of NHP Anesthetized Animal

Eye/Face/Mucous Membrane Protections:

Anesthetized animals in sealed microisolator cage, safety glasses and surgical mask should be worn.

Alternative, if available:

n/a

For puncture and lacerations with a contaminated instrument: Cleanse the wound immediately with a Betadine sponge scrub for 15 minutes. Rinse thoroughly. Notify the employee’s supervisor and the veterinarian responsible for the animal. Report to ROHP, BUOHC, or the BMC Emergency Department after initiating treatment for the full 15 minutes.

For a splash of potentially contaminated fluid to the nose, mouth, or eyes: Flush the site for 15 minutes with water or saline solution. Notify the employee’s supervisor and the veterinarian responsible for the animal. Report to ROHP, BUOHC, or the BMC Emergency Department immediately after flushing for the full 15 minutes.

Description of Common Non-Human Primate Procedures at BUMC and Required Eye/Face Personal

NHP Cage Changing

Eye/Face/Mucous Membrane Protections:

Goggles and surgical mask

Alternative, if available:

Safety glasses, face shield and surgical mask

NHP Dental Cleaning

Eye/Face/Mucous Membrane Protections:

Goggles and surgical mask

Alternative, if available:

n/a

NHP Live Animal Transport or Removal to Transport Cage

Eye/Face/Mucous Membrane Protections:

Goggles and surgical mask

Alternative, if available:

Safety glasses, face shield and surgical mask

Anesthetized NHP Animal transport

Eye/Face/Mucous Membrane Protections:

Goggles and surgical mask

Alternative, if available:

Safety glasses, face shield and surgical mask

NHP Surgery on Anesthetized Animal using Surgical Microscope

Eye/Face/Mucous Membrane Protections:

Safety Glasses (prescription if needed) with Surgical Loupes, Surgical Mask for Lead Surgeon. All surgical assistants in room should wear goggles and surgical mask .

Alternative, if available:

Lead surgeon currently wearing prescription eyeglasses with side shields and surgical loupes over the glasses with a surgical mask. Alternatively, surgical assistants can wear safety glasses, face shield, and surgical mask.

NHP Surgery on Anesthetized Animal using Surgical Loupes

Eye/Face/Mucous Membrane Protections:

Safety Glasses (prescription if needed) with Surgical Loupes, Surgical Mask for Lead Surgeon. All surgical assistants in room should wear goggles and surgical mask.

Alternative, if available:

Lead surgeon currently wearing prescription eyeglasses with side shields and surgical loupes over the glasses with a surgical mask. Alternatively, surgical assistants can wear safety glasses, face shield, and surgical mask.

Tracheal Tube Insertion and Removal during the beginning and end of NHP Surgery

Eye/Face/Mucous Membrane Protections:

Goggles and surgical mask.

Alternative, if available:

Safety glasses (prescription if needed), face shield and surgical mask.

Perfusion of NHP at Termination Surgery

Eye/Face/Mucous Membrane Protections:

Completed in Fume Hood by Lead Surgeon: Involves slicing of heart ventricles, NHP anesthetized.

Alternative, if available:

Completed in Fume Hood by Lead Surgeon: Currently wears prescription eyeglasses and surgical loupes and surgical mask.

Magnetic Resonance Imaging of NHP Anesthetized Animal

Eye/Face/Mucous Membrane Protections:

Anesthetized animals in sealed microisolator cage, safety glasses and surgical mask should be worn.

Alternative, if available:

n/a

II. Introduction/Background: A. Cercopithecine herpes virus 1 (CHV1), also known as B-virus, occurs naturally in macaque monkeys. The virus is enzootic among Old World macaques and usually causes minimal or undetectable morbidity in its natural host. Employees who have contact with these animals’ tissues or secretions, may be exposed to B-virus through bites, scratches, cuts, contaminated needle-sticks and other contact of mucous membranes or broken skin with infected body fluids from macaques or with wet, unfixed tissues or primary cell culture material. In addition contaminated husbandry and research equipment can potentially spread B-virus.

B. Persons exposed to contact with blood, tissue or secretions of nonhuman primates are at risk for B-virus infection through:

1. Bites
2. Eye splash
3. Mucous membrane exposure
4. Contaminated needle-sticks
5. Exposure of cuts or broken skin to contaminated material.
6. Scratch from an animal or cage/equipment
7. Exposure at necropsy (i.e., cut from a scalpel blade)
8. Saliva contamination of an existing wound
9. Exposure to infections tissue or fluids of NHP (i.e., , ocular, oral, genital secretions CNS tissue and CSF), that are potentially infectious.
10. Exposure of broken skin to primary cell cultures de-rived from macaque kidneys are a potential source of virus.
11. Human-to-human transmission (i.e., cleaning of a contaminated wound )

III. Pre-exposure Requirements for Employees

1. Contact Research Occupational Health for screening and approval for any work that may involve direct or indirect contact with non-human primates or non-human primate fluids, blood or tissue.
2. Training is required for those working with NHP and NHP tissue: a.Classroom training: Herpes B virus and Working Safely with NHP training session b. If applicable, demo bite kit and eye wash stations tour c. Demonstration of PPE entry procedures d. Supplemental reading material may be provided; refer to attending veterinarian for questions e. Post- exposure instructions handouts provided during training sessions
3. Personal Protective Equipment (PPE): a. Protective eyewear (e.g. goggles or glasses with solid side shields). b. Face Shield (must be able to prevent splashes to the head from running down into the eyes c. Face mask d. Disposable Lab coat +/- Scrubs e. Disposable Jump Suits (if in street clothes or Quarantine room entry) f. Gloves ( 2 pairs ) g. Sleeve covers h. Shoe covers i. Hair bonnet

IV. Post-exposure Procedure Recommendations for Employees

Stop, Wash, Report

A. Stop: If injured or exposed STOP what you are doing.

B. Wash:

1. IMMEDIATELY Scrub or irrigate wounds or scratches for 15 minutes contact time. a. Flush and scrub with chlorhexidine or Providine –iodine surgical scrub brush and high volume of water for 15 minutes. Mechanical scrubbing of the wound margins is recommended in addition to the use of copious flowing water and chlorhexidine or Providine – iodine scrub to further cleanse the wound of contamination. (Deep wounds should be gently massaged to increase contact with cleaning solution). b. Mucous membrane exposures (eye, nose, or mouth): Irrigate or flush for 15 minutes with sterile 0.9 sodium chloride irrigation solution or sterile eye irrigating solution or water from eye wash stations (preferably at an eye wash station located in Labs or NHP animal facility). Never use any soap or disinfectants in eyes.

V. First Aid/Post Exposure Prophylaxis

Perform one of the following actions:

For post exposure prophylaxis, individuals thought to be at high risk for infection following a bite, laceration, or puncture wound when working with infected neural tissue are administered antivirals. Prophylaxis is started as soon as possible after exposure (within hours), but only after wound cleaning has been completed. The time spent scrubbing or soaking the wound (15 to 20 minutes) is much more important for limiting/preventing transmission, than the type of solution used. Three orally administered agents are currently available for post exposure prophylaxis of CHV-1 infection: acyclovir, valacyclovir, and famciclovir. The drug of choice is valacyclovir 1gram orally every 8 hours for 14 days.

VI. Treatment

If patient is symptomatic, intravenous antiviral therapy with acyclovir or ganciclovir is recommended until symptoms resolve and two cultures over 2 week period are negative. Treatment may be followed by long term suppressive therapy with oral antivirals.

VII. Baseline/Day of Injury Samples

A. Obtain 5-7ml red top tube for B virus serum testing. In the “Miscellaneous Test Request” section of the laboratory requisition; indicate the following tests to be completed: B –Virus – coded as HBVSQ (blood test) and if open wound a swab culture for human virology coded as – HBVCQ.

B. A National B Virus Resource Center Viral Immunology submission form will need to be completed and included with the samples (addendum 3) or electronic copy can be obtained via http://biotech.gsu.edu/virology/PDFs/2015%20Submission%20Form.pdf). BMC Microbiology Supervisor will need to be contacted to inform them that a specimen is being sent over for the patient as well as the primate to be shipped via FedEx to the National B Virus state lab. The primates ID will need to be included in the National B Virus Resource Center Viral Immunology submission form. The following link provides specific shipping instructions for both the patient and primate specimens: http://biotech.gsu.edu/virology/PDFs/2012%20Sample%20Collect%20&%20Shipmt.pdf

Non-human primate specimen requirements obtained by the Laboratory Animal Science Center:

A. Primate baseline serum (0.5 – 2.0 ml) collected as close as possible to the time of injury. B. Primate virology swab samples of the buccal cavity, right eye, left eye, and genitalia. Please use one swab per site and send in separate media tubes. These specimens must be collected as close as possible to the time of injury, as specimens collected later may not accurately reflect the monkey’s status at time of injury.

VIII. Follow-up/14 – 21 Day Post Injury Samples Obtain 5-7ml red top tube for B virus serum testing. In the miscellaneous test request section of the laboratory requisition indicate the following tests to be completed: B –Virus – coded as HBVSQ (blood test) and if open wound a swab culture for human virology coded as – HBVCQ. A National B Virus Resource Center Viral Immunology submission form will need to be completed and included with the samples or electronic copy can be obtained via http://biotech.gsu.edu/virology/PDFs/2015%20Submission%20Form.pdf). BMC Microbiology Supervisor will need to be contacted to inform them that a specimen is being sent over for the patient as well as the primate to be shipped to the National B Virus state lab. The primates ID will need to be included in the National B Virus Resource Center Viral Immunology submission form. The following link provides specific shipping instructions for both the patient and primate specimens: http://biotech.gsu.edu/virology/PDFs/2012%20Sample%20Collect%20&%20Shipmt.pdf.

And follow-up of serum for Herpes B Virus at 30 days post completion of antiviral medication.

IX. Reporting:

A. The ROHP practitioner will send an email notification regarding the incident to Boston University, Office of Research Compliance key stakeholders.

B. Complete the Boston Public Health Commission Research Laboratory Reporting Form or a PDF on-line filler copy of the form which can be obtained via https://www.pdffiller.com/55218182-Biologic_Research_Laboratory_Reporting_Form_3-13pdf-Biologic-Research-Laboratory-Reporting-Form—Boston-Public–Various-Fillable-Forms . A telephone call to the Boston Public Health Commission should be made to inform of incident followed by a faxed copy of the report: (617) 534-2814 (tel), (617) 534-5905 (fax).

Environmental Health and Safety will conduct a follow-up investigation of the exposure.

X. References:

1. CDC (Centers for Disease Control and Prevention). B Virus (herpes B, monkey B virus, herpesvirus simiae, and herpesvirus B). http://www.cdc.gov/herpesbvirus/index.html
2. National B Virus Resource Center. http://biotech.gsu.edu/virology/
3. CDC (Centers for Disease Control and Prevention). 1987. Guidelines for the Prevention of Herpesvirus simiae (B Virus) Infection in Monkey Handlers. Morbidity and Mortality Weekly Report (MMWR) 36 (41): 680-682, 687-689; October 23, 1987.
4. Cohen, Jeffrey I., et al. Recommendations for Prevention of and Therapy for Exposure to B Virus (Cercopithecinec Herpesvirus 1). Clinical Infectious Diseases 2002; 35:1191-1203. http://www.ncbi.nlm.nih.gov/pubmed/12410479
5. CME Resource. Zoonotic Diseases. Prevention and Nursing Care. January 2001, Vol 73, No.2. Holmes, et. al. Guidelines for the Prevention and Treatment of B-virus Infections in Exposed Persons. Clinical Infectious Diseases 1995; 20:421-439.
6. Cercopithecine herpesvirus 1 (B Virus) infection resulting from ocular exposure. NOISE, May 1999. Publication No. 99-100. http://www.cdc.gov/niosh/docs/99-100/ Reviewed 11/27/02. Revised: 6/19/07, 7/08
7. Biosafety in Microbiological and Biomedical Laboratories 5th edition. https://www.cdc.gov/biosafety/publications/bmbl5/index.htm
8. Mandell, G. L., J. E. Bennett, et al. (2010). Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. Philadelphia, PA, Churchill Livingstone/Elsevier.

Biosafety in Microbiological and Biomedical Laboratories (BMBL) 6th Edition

Public Health Canada: Material Safety Data Sheets – Infectious Substances

American Biologic Safety Association

American Biologic Safety Association (ABSA) Risk Group Classification

Agency for Toxic Substances and Disease Registry (ATSDR)

National Medical Library: TOXNET

Environmental Health & Toxicology Specialized Information Services (HHS)

OSHA Carcinogens

Text Modified from Document Created by Michael S. Rand, DVM, ACLAM Occupational Health in the Care and Use of Research Animals, Institute of Laboratory Research (ILAR): National Academy Press, 1997.

Boston Public Health Commission

National Institute for Occupational Safety and Health

Occupational Safety and Health Administration

American College of Occupational and Environmental Medicine

American Association of Occupational Health Nurses, INC.

Centers for Disease Control and Prevention