Section VII—Occupational Health and Immunoprophylaxis
The goal of medical support services in a biomedical research setting is to promote
a safe and healthy workplace. This is accomplished by limiting opportunities for
exposure, promptly detecting and treating exposures, and using information
gained from work injuries to further enhance safety precautions. Occupational
health and safety in biomedical research settings is a responsibility shared by
healthcare providers, safety specialists, principal investigators, employers, and
workplace personnel. Optimal worker protection depends on effective, ongoing
collaboration among these groups. Supervisors, working with personnel
representatives, should describe workers’ proposed tasks and responsibilities.
First line supervisors and safety professionals should identify the potential
worksite health hazards. Principal investigators may serve as subject matter experts.
The health provider should design medical support services in consultation with
representatives from the institutional environmental health and safety program
and the principal investigators. Workers should be fully informed of the available
medical support services and encouraged to utilize them. Requisite occupational
medical services are described below and expanded discussions of the principles
of effective medical support services are available in authoritative texts.1,2
Services offered by the medical support team should be designed to be in
compliance with United States Department of Labor (DOL), OSHA regulations,
patient confidentiality laws, and the Americans with Disabilities Act of 1990.3-8
Medical support services should be based upon detailed risk assessments and
tailored to meet the organization’s needs. Risk assessments should define
potential hazards and exposures by job responsibility. They should be provided
for all personnel regardless of employment status. Contracted workers, students,
and visitors should be provided occupational medical care by their employer
or sponsor equivalent to that provided by the host institution for exposures,
injuries, or other emergencies experienced at the worksite.
Occupational medical services may be provided through a variety of
arrangements (e.g., in-house or community based) as long as the service is
readily available and allows timely, appropriate evaluation and treatment. The
interaction between worker, healthcare provider and employer may be complex,
such as a contract worker who uses his own medical provider or uses contract
medical services. Thus, plans for providing medical support for workers should
be completed before work actually begins. The medical provider must be
knowledgeable about the nature of potential health risks in the work
environment and have access to expert consultation.
Prevention is the most effective approach to managing biohazards.
Prospective workers should be educated about the biohazards to which they
may be occupationally exposed, the types of exposures that place their health
at risk, the nature and significance of such risks, as well as the appropriate first
aid and follow up for potential exposures. That information should be reinforced
114
Biosafety in Microbiological and Biomedical Laboratories
annually, at the time of any significant change in job responsibility, and following
recognized and suspected exposures.9-11
Medical support services for biomedical research facilities should be
evaluated annually. Joint annual review of occupational injury and illness reports
by healthcare providers and environmental health and safety representatives
can assist revision of exposure prevention strategies to minimize occupational
health hazards that cannot be eliminated.
Occupational Health Support Service Elements
Preplacement Medical Evaluations
Workers who may be exposed to human pathogens should receive a
preplacement medical evaluation. Healthcare providers should be cognizant of
potential hazards encountered by the worker. A description of the requirements
for the position and an understanding of the potential health hazards present in
the work environment, provided by the worker’s supervisor, should guide the
evaluation. The healthcare provider should review the worker’s previous and
ongoing medical problems, current medications, allergies to medicines, animals,
and other environmental proteins, and prior immunizations. With that information,
the healthcare provider determines what medical services are indicated to permit
the individual to safely assume the duties of the position. Occasionally, it may
be useful to review pre-existing medical records to address specific concerns
regarding an individual’s medical fitness to perform the duties of a specific position.
If pre-existing medical records are unavailable or are inadequate, the healthcare
provider may need to perform a targeted medical exam. Comprehensive physical
examinations are rarely indicated. During the visit, the healthcare provider should
inform the worker of potential health hazards in the work area and review steps
that should be taken in the event of an accidental exposure. This visit also
establishes a link with the medical support services provider.
When occupational exposure to human pathogens is a risk, employers
should consider collecting and storing a serum specimen prior to the initiation of
work with the agent. It can be used to establish baseline sero-reactivity, should
additional blood samples be collected for serological testing subsequent to a
recognized or suspected exposure.
Occasionally, it is desirable to determine an individual’s vulnerability to infection
with specific agents prior to assigning work responsibilities. Some occupational
exposures present substantially more hazard to identifiable sub-populations of
workers. Immunodeficient workers or non-immune pregnant female workers may
experience devastating consequences from exposures that pose a chance of risk
to pregnant women with prior immunity and other immunocompetent workers
(e.g., cytomegalovirus or toxoplasmosis). Serologic testing should be used to
document baseline vulnerability to specific infections to which the worker might
Occupational Health and Immunoprophylaxis
115
be exposed, and non-immune workers should be adequately informed about
risks. In specific settings, serologic documentation that individual workers
have pre-existing immunity to specific infections also may be required for
the protection of research animals.10
Vaccines
Commercial vaccines should be made available to workers to provide protection
against infectious agents to which they may be occupationally exposed.12-16 The
Advisory Committee on Immunization Practices (ACIP) provides expert advice
to the Secretary of the DHHS, the Assistant Secretary for Health, and the CDC
on the most effective means to prevent vaccine-preventable diseases and to
increase the safe usage of vaccines and related biological products. The ACIP
develops recommendations for the routine administration of vaccines to pediatric
and adult populations, and schedules regarding the appropriate periodicity,
dosage, and contraindications. The ACIP is the only entity in the federal
government that makes such recommendations. The ACIP is available at
the CDC Web site: www.cdc.gov.
If the potential consequences of infection are substantial and the protective
benefit from immunization is proven, acceptance of such immunization may be
a condition for employment. Current, applicable vaccine information statements
must be provided whenever a vaccine is administered. Each worker’s immunization
history should be evaluated for completeness and currency at the time of
employment and re-evaluated when the individual is assigned job responsibilities
with a new biohazard.
When occupational exposure to highly pathogenic agents is possible and
no commercial vaccine is available, it may be appropriate to immunize workers
using vaccines or immune serum preparations that are investigational, or for
which the specific indication constitutes an off-label use. Use of investigational
products, or of licensed products for off-label indications must be accompanied
by adequate informed consent outlining the limited availability of information
on safety and efficacy. Use of investigational products should occur through
Investigational New Drug (IND) protocols providing safety oversight by both the
Food and Drug Administration (FDA) and appropriate Institutional Human Subjects
Research Protection Committees.17,18 Recommendation of investigational
products, as well as commercial vaccines that are less efficacious, associated
with high rates of local or systemic reactions, or that produce increasingly severe
reactions with repeated use, should be considered carefully. Receipt of such
vaccines is rarely justified as a job requirement.
Investigational vaccines for eastern equine encephalomyelitis (EEE) virus,
Venezuelan equine encephalitis (VEE) virus, western equine encephalomyelitis
(WEE) virus, and Rift Valley fever viruses (RVFV), may be available in limited
116
Biosafety in Microbiological and Biomedical Laboratories
quantities and administered on-site at the Special Immunization Program, United
States Army Medical Research Institute of Infectious Diseases (USAMRIID).
Periodic Medical Evaluations
Routine, periodic medical evaluations generally are not recommended; however,
limited periodic medical evaluations or medical clearances targeted to job
requirements may occasionally be warranted (e.g., respirator usage).3 In
special circumstances, it may be appropriate to offer periodic laboratory
testing to workers with substantial risk of exposure to infectious agents to
detect pre-clinical or sub-clinical evidence for an occupationally acquired
infection. Before asymptomatic workers without specific exposures are tested
for seroreactivity, the benefit of such testing should be justified, plans for further
investigation of indeterminate test results should be delineated, and clearly
defined criteria for interpretation of results should be developed.
Medical Support for Occupational Illnesses and Injuries
Workers should be encouraged to seek medical evaluation for symptoms that
they suspect may be related to infectious agents in their work area, without fear
of reprisal. A high index of suspicion for potential occupational exposures should
be maintained during any unexplained illness among workers or visitors to
worksites containing biohazards. Modes of transmission, as well as the clinical
presentation of infections acquired through occupational exposures, may differ
markedly from naturally acquired infections. Fatal occupational infections have
resulted from apparently trivial exposures. The healthcare provider should have
a working understanding of the biohazards present in the workplace and remain
alert for subtle evidence of infection and atypical presentations. A close working
relationship with the research or clinical program in which the affected employee
works is absolutely essential. In the event of injury, consultation between
healthcare provider, employee, and the employee’s supervisor is required
for proper medical management and recordkeeping.
All occupational injuries, including exposures to human pathogens, should
be reported to the medical support services provider. Strategies for responding
to biohazard exposures should be formulated in advance. Proper post-exposure
response is facilitated by exposure-specific protocols that define appropriate first
aid, potential post-exposure prophylaxis options, recommended diagnostic tests,
and sources of expert medical evaluation. These protocols should address how
exposures that occur outside of regular work hours are handled and these
protocols should be distributed to potential healthcare providers (e.g., local
hospital emergency departments). In exceptional cases, the protocols should
be reviewed with state and community public health departments. Emergency
medical support training should be provided on a regular basis for both
employees and healthcare providers.
Occupational Health and Immunoprophylaxis
117
The adequacy and timeliness of wound cleansing or other response after
an exposure occurs may be the most critical determinant in preventing infection.
First aid should be defined, widely promulgated, and immediately available to an
injured worker. Barriers to subsequent medical evaluation and treatment should
be identified and minimized to facilitate prompt, appropriate care. Laboratory
SOPs should include a printed summary of the recommended medical response
to specific exposures that can guide immediate response in the work place and
that the injured worker can provide to the treating facility. The medical provider’s
description of the injury should include:
■■
The potential infectious agent.
■■
The mechanism and route of exposure (percutaneous, splash to
mucous membranes or skin, aerosol, etc.).
■■
Time and place of the incident.
■■
Personal protective equipment used at the time of the injury.
■■
Prior first aid provided (e.g., nature and duration of cleaning and
other aid, time that lapsed from exposure to treatment).
■■
Aspects of the worker’s personal medical history relevant to risk
of infection or complications of treatment.
First aid should be repeated if the initial adequacy is in question. Healthcare
providers must use appropriate barrier precautions to avoid exposure to
infectious agents and toxins.
In some instances, it may be possible to prevent or ameliorate illness
through post-exposure prophylaxis. Protocols should be developed in advance
that clearly identify the situations in which post-exposure prophylaxis are to be
considered, the appropriate treatment, and the source of products and expert
consultation. Accurate quantification of risk associated with all exposures is not
possible, and the decision to administer post-exposure prophylaxis may have
to be made quickly and in the absence of confirmatory laboratory testing. Postexposure regimens may involve off-label use of licensed products (e.g., use of
smallpox vaccine for workers exposed to monkeypox) in settings where there is
insufficient experience to provide exact guidance on the safety or likely protective
efficacy of the prophylactic regimen. Thus, protocols should exist that delineate
the circumstances under which it would be appropriate to consider use of each
product following exposure, as well as the limits of our understanding of the
value of some post-exposure interventions. In these cases, consultations with
subject matter experts are especially useful.
Estimating the significance of an exposure may be difficult, despite having
established protocols. The clinician may need to make a “best-estimate” based
118
Biosafety in Microbiological and Biomedical Laboratories
upon knowledge of similar agents, exposure circumstances, and advice received
from knowledgeable experts. Appropriate post-exposure prophylactic response
is always pathogen and exposure dependent, and may be host-factor dependent
and influenced by immediate post-exposure management. Before prophylactic
treatment is undertaken, confirm the likelihood that an exposure occurred, that
prophylaxis is indicated and is not contraindicated by past medical history.
Conveying this information to the injured worker requires clear, honest
communication. The clinical risk assessment and treatment decision process
should be carefully explained, the worker’s questions addressed with relevant,
preprinted educational materials provided. Prompt treatment should be provided,
with a mutually agreed plan to follow the individual’s clinical course.
The applicable workers compensation claim form should be provided
with appropriate explanations for its completion. The supervisor must receive a
description of the accident or incident, confirm the circumstances of the injury
or exposure and provide relevant advice. The report also should be distributed
to all other relevant parties, such as the safety professional. Each incident
should receive prompt reconsideration of the initial risk assessment and
reevaluation of current strategies to reduce the possibility of future exposures.
Post-exposure serologic testing may be useful, but it is important to determine
how information obtained from serologic testing will be interpreted. It is also
essential to collect serum specimens at the appropriate interval for a given
situation. Assessment of sero-reactivity in exposed workers is most helpful when
the results of specimens collected over time can be compared. Ideally specimens
collected prior to, at the time of and several weeks following exposure, should be
tested simultaneously and results compared to assess changes in the pattern of
sero-reactivity. Serum collected too early after exposure may fail to react even
when infection has occurred, because antibodies have not yet been produced in
detectable quantities. When immediate institution of post-exposure prophylaxis
may delay seroconversion, or when the agent to which the worker was exposed
results in seroconversion completed over months (e.g., retroviruses), testing of
specimens collected late after exposure is particularly important.
Testing of a single serum specimen is generally discouraged and can result
in misinterpretation of nonspecific sero-reactivity. Evidence of sero-conversion
or a significant (≥ 4 fold) increase in titer associated with a compatible clinical
syndrome is highly suggestive of acute infection.
However, the significance of and appropriate response to sero-conversion in
the absence of illness is not always clear. If sero-reactivity is evident in the earliest
specimen, it is important to re-test that specimen in tandem with serum specimens
archived prior to occupational exposure and/or collected serially over time to
investigate whether a change in titer suggestive of new infection can be identified.
Occupational Health and Immunoprophylaxis
119
In some exposure situations, it may be appropriate to store serially collected
serum samples, and to send them for testing as evidence of seroconversion only
if symptoms develop that suggest an infection may have occurred (e.g., Monkey
B virus exposures). Serum collected at the time of employment, and any other
specimens not immediately tested should be stored frozen at a temperature of
-20º C or lower in a freezer that does not experience freeze-thaw cycles. An
inventory system should be established to ensure the accurate and timely
retrieval of samples, while protecting patient privacy.
When investigational or other non-commercial assays are utilized, the
importance of appropriate controls and the ability to compare serially collected
specimens for quantification/characterization of reactivity is increased. The
availability of aliquoted samples that allow additional testing may be essential
to assist interpretation of ambiguous results. Caution should be taken to avoid
placing more confidence in testing outcomes than can be justified by the nature
of the assays.
Occupational Health in the BSL-4 Setting
Work with BSL-4 agents involves special challenges for occupational health.
Infections of laboratory staff by such agents may be expected to result in
serious or lethal disease for which limited treatment options exist. In addition,
BSL-4 agents are frequently geographically exotic to the areas in which high
containment labs are located but produce immediate public health concern if
infections occur in laboratory staff. Potential (if unlikely) transmission from
infected staff into the human or animal populations in the areas surrounding the
laboratories may raise such concerns to higher levels. Thus, SOPs for BSL-4
settings require special attention to management of unexplained worker absence,
including protocols for monitoring, medical evaluation, work-up, and follow-up
of workers with unexplained nonspecific illness. Advance planning for the
provision of medical care to workers potentially infected with BSL-4 agents is a
fundamental component of an occupational health program for a BSL-4 facility.
References
1.
2.
3.
120
Menckel E, Westerholm P, editors. Evaluation in occupational health
practice. Oxford: Butterworth-Heinemann; 1999.
Levy B, Wegman DH, editors. Occupational health: recognizing and
preventing work-related disease and injury, 4th ed. Philadelphia: Lippincott
Williams & Wilkins; 2000.
Occupational Safety and Health Administration (www.osha.gov).
Washington, DC: The Administration. Applicable OSHA Laws,
Regulations and Interpretations; [about 2 screens]. Available at:
www.osha.gov/comp-links.html.
Biosafety in Microbiological and Biomedical Laboratories
4. American Medical Association (www.ama-assn.org). Chicago: The Association;
1995-2006 [updated 2005 Mar 7]. Patient Confidentiality; [about 6 screens]
Available at: www.ama-assn.org/ama/pub/category/4610.html.
5. United States Department of Justice (www.usdoj.gov). Washington, DC: The
Department; [updated 2006 July 28]. American Disabilities Act; [about seven
screens] Available at: http://www.usdoj.gov/crt/ada/adahom1.htm.
6. Occupational Safety and Health Act of 1970, Pub. L. No. 91-596, 84 Stat.
1590 (December 29, 1970).
7. Non-mandatory Compliance Guidelines for Hazard Assessment and Personal
Protective Equipment Selection, 29 CFR Part 1910 Subpart I App B (1994).
8. Multi-Employer Citation Policy, C.P.L. 02-00-124 (1999).
9. National Research Council (US), Committee on Occupational Safety and
Health in Research Animal Facilities, Institute of Laboratory Animal
Resources, Commission on Life Sciences. Occupational health and safety
in the care and use of research animals. Washington, DC: The National
Academies Press; 1997.
10. National Research Council (US), Committee on Occupational Health and
Safety in the Care and Use of Nonhuman Primates, Institute for Laboratory
Animal Research, Division on Earth and Life Studies. Occupational health
and safety in the care and use of nonhuman primates. Washington, DC:
National Academy Press; 2003.
11. Cohen JI, Davenport DS, Stewart JA, et al. Recommendations for prevention
of and therapy for exposure to B virus (cercopithecine herpesvirus 1). Clin
Infect Dis 2002;35:1191-203.
12. Atkinson WL, Pickering LK, Schwartz B, et al. General recommendations on
immunization. Recommendations of the Advisory Committee on
Immunization Practices (ACIP) and the American Academy of Family
Physicians (AAFP). MMWR Recomm Rep. 2002;51:1-35.
13. Centers for Disease Control and Prevention. Update on adult immunization.
Recommendations of the immunization practices advisory committee (ACIP).
MMWR Recomm Rep. 1991;40:1-94.
14. Centers for Disease Control and Prevention. Immunization of health-care
workers: recommendations of the Advisory Committee on Immunization
Practices (ACIP) and the Hospital Infection Control Practices Advisory
Committee (HICPAC). MMWR Morb Mortal Wkly Rep. 1997;46:1-42.
15. Centers for Disease Control and Prevention. Use of vaccines and immune
globulins in persons with altered immunocompetence. Advisory Committee
on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 1993 Apr
9;42(RR-04):1-18.
16. Centers for Disease Control and Prevention. Update: vaccine side effects,
adverse reactions, contraindications, and precautions. Recommendations of
the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm
Rep. 1996 Sep 6; 45(RR-12):1-35. Erratum in: MMWR Morb Mortal Wkly
Rep. 1997;46:227.
Occupational Health and Immunoprophylaxis
121
17. United States Department of Health and Human Services (www.dhhs.gov).
Washington, DC: The Department; [updated 2006 Mar 6]. Office of
Human Research Protections Guidance; [about two screens]. Available
at: http://www.hhs.gov/ohrp.
18. United States Food and Drug Administration (www.fda.gov). Rockville, MD;
The Administration; [updated 2005 June 13]. Information on Submitting an
Investigational New Drug Application for a Biological Product [about three
screens] Available at: http://www.fda.gov/cber/ind/ind.htm.
122
Biosafety in Microbiological and Biomedical Laboratories
