Current Trends Human T-Lymphotropic Virus Type III/
Lymphadenopathy-Associated Virus: Agent Summary Statement
INTRODUCTION
In March 1984, CDC and the National Institutes of Health (NIH),
in
consultation with scientists, physicians, and public health workers
in
academia, industry, and government, published a manual entitled
'Biosafety in
Microbiological and Biomedical Laboratories' ("biosafety manual") *
(1). The
manual describes combinations of standard and special microbiologic
practices, safety equipment, and facilities recommended for working
with
infectious agents in various laboratory settings. The
recommendations are
advisory and provide a voluntary code of safety practices.
A section of this manual is devoted to a number of specific
"agent
summary statements" consisting of brief descriptions of documented
or
anecdotal laboratory-associated infections, the nature of the
laboratory
hazards, and recommended precautions to be taken in handling and
working with
certain infectious agents. Contributors to the manual recognized
that new
agents would be discovered from time to time and recommended that a
summary
statement for each new agent be developed and published in the
MMWR. The
summary statement for human T-lymphotropic virus type
III/lymphodenopathy-
associated virus (HTLV-III/LAV) ** follows. All laboratory
directors are
requested to put a copy of this summary in each of their copies of
the
biosafety manual and bring it to the attention of laboratory
personnel. The
recommendations in the summary statement were compiled from
published
scientific reports and are consistent with the published guidelines
for
health-care workers (2-4).
AGENT SUMMARY STATEMENT: HTLV-III/LAV
As of August 15, 1986, no cases of acquired immunodeficiency
syndrome
(AIDS) that meet the CDC case definition and can be attributed to
an
inadvertent laboratory exposure have been reported in laboratory
workers (5).
One laboratory worker (7) was included among the health-care
workers who have
had HTLV-III/LAV antibody detected in their serum after sustaining
a
needlestick injury (2,3,6-10), but the source of the infection
could not be
established. Persons who are infected with HTLV-III/LAV may be
asymptomatic,
may have AIDS-related complex, or may manifest symptoms of overt
AIDS (11).
In 1985, two different reagent production laboratories reported
that
several laboratory workers may have been inadvertently exposed to
an aerosol
of concentrated HTLV-III/LAV; one worker was cut by a piece of
glass from a
broken carboy that contained HTLV-III/LAV-infected cells and
culture fluid.
None of the potentially exposed persons had shown evidence of
seroconversion
after 6 months in one incident and 12 months in the other as a
result of
these occupational exposures.
Other reports dealing with HTLV-III/LAV infection in
health-care
personnel, including laboratory workers (3,4,6,8-10), indicate that
the risk
of bloodborne transmission from inadvertent exposure is
considerably less for
HTLV-III/LAV than for hepatitis B virus infection. These reports
illustrate
the need for complete evaluation by a physician and serologic
testing of each
laboratory worker definitely or possibly exposed to HTLV-III/LAV in
a
laboratory setting. It is recommended that the Public Health
Service
guidelines for health-care workers be followed in these instances
(2,3).
Laboratory Hazards
HTLV-III/LAV has been isolated from blood, semen, saliva,
tears, urine,
cerebrospinal fluid, brain tissue, and cervical secretions and is
likely to
be present in other body fluids, secretions, and tissues of
infected humans
or experimentally infected nonhuman primates. Percutaneous or
parenteral
inoculation and direct contact of cuts, scratches, abrasions, or
mucosal
surfaces with suspensions of virus or specimens containing live
virus are
considered potential routes of infection. Possible transmission of
infection
via the parenteral route can occur through self-inoculation with
needles,
broken glass, or other sharp objects that contain HTLV-III/LAV.
Spillage is
a possible means of exposure and infection, especially spills
accompanied by
spraying or splashing of infected cell cultures, viral
concentrates, and
other infectious materials that may come into direct contact with
abraded
skin or mucous membranes of the eyes, nose, or mouth; however,
there are no
data documenting or suggesting that transmission of HTLV-III/LAV
has occurred
in this manner. Ingestion and inhalation have not been documented
as modes of
transmission of the virus.
Recommended Precautions
Biosafety Level (BSL) 2 standards and special practices,
containment
equipment, and facilities as described in the CDC-NIH biosafety
manual
are recommended for activities involving clinical specimens,
body fluids,
or tissues from humans or laboratory animals that may contain
HTLV-III/
LAV. These are the same practices recommended for all clinical
specimens.
Emphasis is placed on the following practices, which are
included in the
manual (1):
Use of syringes, needles and other sharp instruments should
be
avoided if possible. Used needles and cutting instruments
should be
discarded into a puncture-resistant container with a lid.
Needles
should not be resheathed, purposefully bent, broken,
removed from
disposable syringes, or otherwise manipulated by hand.
Gloves should be worn by all personnel engaged in
activities that may
involve skin contact with potentially infectious fluids,
tissues, or
cultures and by laboratory workers with dermatitis or other
lesions
on the hands who may have direct or indirect contact with
potentially
infectious materials. Handwashing with soap and water
should be a
routine practice immediately after direct contact with
potentially
infectious materials and on completion of work, even when
gloves are
worn.
Generation of aerosols, splashes, and spills of potentially
infectious materials should be avoided in procedures
involving body
fluids or tissues, during necropsy of cadavers, and in
similar
procedures on animals experimentally infected with
HTLV-III/LAV.
Laboratory workers should use a biological safety cabinet
when
propagating the virus to further reduce the risk of
exposure.
Although the major precautions are listed here, the CDC-NIH
biosafety
manual contains additional related precautions (see pages
11-13 for
BSL 2 and pages 14-17 (1) for BSL 3 when large volumes or
concen-
trates of HTLV-III/LAV are involved). In all instances, the
laboratory director is responsible for assessing the
biosafety level
to be used.
Human serum from any source that is used as a control or
reagent in
a test procedure should be handled at BSL 2 (see pages
11-13 (1)).
Appended to this Agent Summary Statement is a statement
(Addendum 1)
issued by CDC on the use of all human control or reagent
sera shipped
to other laboratories. The Food and Drug Administration
requires that
manufacturers of human serum reagents use a similarly
worded
statement.
Animal BSL 2 practices, containment equipment, and
facilities are
recommended for activities involving nonhuman primates
experimentally
infected with HTLV-III/LAV. Laboratory coats, gowns, or
uniforms
should be worn by laboratory workers, as is customary for
other BSL
2 or 3 practices, depending on the nature of the work,
concentration
of the virus, and volume of material being handled. Because
many
animals bite, and some throw feces, urine, or expectorate
at humans,
animal-care personnel must wear coats, protective gloves,
coveralls
or uniforms, and face shields as appropriate to protect the
skin and
mucous membranes of the eyes, nose, and mouth from
potential exposure
to these substances when working with animals likely to
manifest such
behavior.
Activities such as growing research-laboratory-scale amounts of
HTLV-
III/LAV or related viruses or virus-producing cell lines,
working with
concentrated virus preparations, or conducting procedures that
may
produce droplets or aerosols should be performed in a BSL 2
facility with
the additional practices and containment equipment recommended
for BSL 3
(12).
Activities involving industrial-scale, large-volume, or
high-concen-
tration production and manipulation of HTLV-III/LAV are to be
conducted
with BSL 3 requirements (12).
All laboratory glassware, equipment, disposable materials, and
wastes
suspected or known to contain HTLV-III/LAV must be
decontaminated,
preferably in an autoclave, before washing, discarding, etc.
Incineration
of solid wastes may be used as an alternate method of disposal.
There is no evidence that laboratory clothing soiled with
materials known
or suspected to contain HTLV-III/LAV poses a transmission
hazard, and the
handling of such clothing is covered under BSL 2 practices.
However, to
be consistent with BSL 3 recommendations (1), when laboratory
clothing
becomes contaminated with HTLV-III/LAV preparations, it should
be
decontaminated before being laundered or discarded.
Work surfaces should be decontaminated at the end of each day
on
completion of procedures or when overly contaminated. Many
commonly used
chemical disinfectants with such active ingredients as sodium
hypo-
chlorite, formaldehyde, glutaraldehyde, or phenols (4, 13-15)
can be used
to decontaminate laboratory work surfaces; they can also be
used to
decontaminate some laboratory instruments, specific areas of
contaminated
laboratory clothing, and spills of infectious materials. Prompt
decontam-
ination of spills and other overt contamination should be
standard
practice.
The prudent and recommended approach to handling human serum
known or
suspected to contain HTLV-III/LAV is to use the same
precautions that
should be used routinely to prevent transmission of bloodborne
infections, including hepatitis B (16). Available data on the
effectiveness of heat to destroy HTLV-III/LAV suspected or
known to be
present in human serum are at variance because of variations in
volume of
serum, concentration of the virus, temperature, and duration of
exposure
to heat (14, 15, 17). Similarly, results of chemical analyses
or antibody
assays may vary when sera are heated before testing according
to the
analysis or assay being performed (18-20). However, there is
agreement
that testing heated serum for HTLV-III/LAV antibody by enzyme
immuno-
assays often yields false-positive results (21-23).
No HTLV-III/LAV vaccine has been developed, and no drugs have
been shown
to be safe and effective for therapy. As part of an ongoing
medical
surveillance program for employees, all laboratory workers
before being
assigned to activities with a high potential for exposure
should have a
serum sample obtained and stored at -40 C (-4Q F) for possible
future
testing. Subsequent serum samples should be obtained and stored
in
accordance with laboratory policy or following an inadvertent
laboratory
exposure involving materials described above. When indicated,
these serum
specimens should be tested by a qualified laboratory using
currently
recommended procedures for HTLV-III/LAV antibody. Furthermore,
the
physician requesting serologic testing of these serum specimens
must
first obtain informed consent from the laboratory worker and
describe the
confidentiality safeguards available to protect test results.
The
laboratory workers whose serum specimens are to be tested
should
understand how the test results are to be used, the
implications of a
positive or negative test result, and the limits, if any, of
the
confidentiality safeguards. An employee whose serum
HTLV-III/LAV antibody
test is reactive and whose subsequent tests and evaluation
confirm the
presence of HTLV-III/LAV infection should be counseled to
follow the
Public Health Service recommendations for preventing
transmission (24,
25).
In addition to HTLV-III/LAV, other primary, as well as
opportunistic,
pathogenic agents may be present in the body fluids and tissues
of
persons who are antibody positive or have AIDS-related complex
or AIDS.
Laboratory workers should follow accepted biosafety practices
to ensure
maximum protection against inadvertent laboratory infection
with agents
other than HTLV-III/LAV that may also be present in clinical
specimens.
Reported by Div of Safety, National Institute of Allergy and
Infectious
Diseases, National Cancer Institute, National Institutes of
Health; AIDS
Program, Hospital Infections Program, Center for Infectious
Diseases,
Laboratory Program Office, Office of Biosafety, Office of the
Director, CDC.
ADDENDUM
CDC cautionary notice for all human serum samples used as controls
or
reagents:
WARNING: Because no test method can offer complete assurance that
laboratory
specimens do not contain HTLV-III/LAV, hepatitis B virus, or other
infectious
agents, this specimen(s) should be handled at the BSL 2 as
recommended for
any potentially infectious human serum or blood specimen in the
CDC-NIH
manual, 'Biosafety in Microbiological and Biomedical Laboratories',
1984,
pages 11-3.
One or more of the following statements should be included with
the above
warning statement:
This specimen is negative for hepatitis B surface antigen
(HBsAg).
This specimen is negative for antibody to HTLV-III/LAV.
This specimen is positive for hepatitis B surface antigen
(HBsAg).
This specimen is positive for antibody to HTLV-III/LAV.
This specimen has NOT been tested for hepatitis B surface
antigen
(HBsAg).
This specimen has NOT been tested for antibody to HTLV-III/LAV.
This specimen has been heated at 56 C (133 F) for 30 minutes
(which will
not inactivate HBsAg but will inactivate HTLV-III/LAV).
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Price:
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** The Human Retrovirus Subcommittee of the International Committee
on the
Taxonomy of Viruses has proposed the name human immunodeficiency
virus (HIV)
for these viruses (Science 1986;232:697).
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