The report of a case of encephalitis caused by B virus in a
handler in 1932 indicated that B virus can be highly pathogenic for
(1). Seventeen additional cases of B virus infection in humans were
described through 1973 (2)* and four cases, including the first
of person-to-person transmission of the virus, occurred in
Florida, in 1987 (5). Twenty of the 22 cases resulted in
of these patients died. This extreme degree of morbidity and
given the impression that B virus infection in humans nearly always
in severe or fatal disease. The frequency of mild or asymptomatic B
infection, however, has never been adequately assessed.
The occurrence of the four 1987 cases of B virus infection
to convene a working group to discuss guidelines for preventing B
infection in monkey handlers. In formulating these guidelines, the
group recognizes that other methods of caring for nonhuman primates
preventing transmission of pathogenic agents from animal to human
human to animal have been described (6,7). The purpose of the
was to supplement existing methods with specific guidelines
minimize transmission of B virus infection from macaque monkeys to
Herpesvirus simiae (B virus) is a member of the herpes group of
that is enzootic in rhesus (Macaca mulatta), cynomolgus (M.
and other Asiatic monkeys of the genus Macaca. As with herpes
I infection in humans, primary infection with B virus in macaques
result in gingivostomatitis with characteristic buccal mucosal
it probably occurs frequently without such signs. Subsequently, the
remains latent in the host and may reactivate spontaneously or in
stress, resulting in shedding of virus in saliva and/or genital
In captivity, as well as in the wild, sexually mature macaques are
likely to have been exposed to the virus and more likely than
animals to be shedding virus at any given time.
Although it is commonly believed that transmission to humans
exposure to contaminated monkey saliva through bites or scratches,
exposure has not been consistently documented. Except for one
person-to-person transmission, however, all cases of B virus
humans have occurred in persons exposed to monkeys or monkey
B virus-related disease is characterized by a variety of
which generally occur within 1 month of exposure. These symptoms
vesicular skin lesions at or near the site of inoculation,
neurologic symptoms, and ultimately, encephalitis.
A unique feature of the 1987 Pensacola cases was the occurrence
disease in two of the four patients (5). Both of these persons
acyclovir (9-((2-hydroxyethoxymethyl))-guanine) in the early stages
disease. They became culture- negative, and their lesions healed
therapy. Whether their infections would have become more severe
therapy is not known. Both in vivo (8) and in vitro efficacy of
(Southwest Foundation for Biomedical Research, unpublished data)
virus has been demonstrated.
The working group recognizes that B virus infection may occur
persons not handling live macaques. One case of B virus infection
following the person's exposure to contaminated cell cultures of
origin, and one case occurred after the patient had cleaned a
(2). Although transmission of infection has not been documented for
working with B virus in the laboratory, such work is potentially
Guidelines concerning appropriate biocontainment measures for
B virus are published elsewhere (9). The guidelines described
pertain only to the risk associated with the care and maintenance
The working group also recognizes that the paucity of
regarding the transmissibility of B virus, the efficacy of measures
prevent transmission, and the chemotherapy of B virus infection
rendered these guidelines difficult to formulate. These guidelines
therefore based on the available information, much of which is
and much of which is based on theoretical considerations from
other herpes viruses.
The risk of acquiring B virus infection from macaques appears
very low. Persons who have handled macaques since B virus infection
first reported in humans number in the thousands, yet only 22
well-documented cases of infection have been described. The reasons
such an apparently low rate of transmission may include infrequent
shedding by macaques, cross-reactive immunity against B virus
herpes simplex virus infection (10,11), and undetected asymptomatic
infection. Nevertheless, the consequences of symptomatic infection
that these guidelines are warranted, especially since such
Guidelines for prevention of B virus infection in monkey handlers:
Macaque monkeys should be used for research purposes only when
When feasible, monkeys that are required for research purposes
be free of B virus infection and should be maintained under
that are appropriate to assure their B virus-free status. The
possibility of acquiring and maintaining such a B virus-free
should be explored by each animal facility.
All macaque monkeys not known to be free of B virus infection
regarded as infected because viral shedding is intermittent and
occur in the absence of visible lesions. Direct handling of
should be minimized as much as possible. Capturing,
otherwise handling fully awake macaques by hand is not
Rather, such procedures should be accomplished using acceptable
physical and chemical restraint methods. Macaques that are
regularly should be housed in squeeze-back cages that permit
restraint of the animal before handling. When a number of
caged together, tunnels or chutes should be provided whenever
so that individual monkeys can be separated and restrained
handling. When feasible, chemical restraint by injection (e.g.,
ketamine HCl) may be used before removing the animal from the
particularly for larger animals or for animals that are
difficult to handle. Behavioral conditioning of macaques is a
and useful adjunct to the application of these restraint
is particularly recommended where several animals are caged
Macaque handlers should remove physically active animals from
only with arm-length reinforced leather gloves. Handlers should
additionally protected with a long-sleeved garment to prevent
and a face shield (or surgical mask and goggles or glasses) to
exposure of eyes and mucous membranes to macaque secretions. In
climates, where use of long-sleeved garments and leather gloves
uncomfortable, supervisors may wish to rotate work schedules or
workers handle animals at cooler times of the day to minimize
discomfort in the daily work routine. If macaque handlers
choose not to
handle chemically restrained animals with arm-length leather
latex or vinyl gloves should be worn to prevent direct contact
Cages and other equipment that may be contaminated with virus
free of sharp edges and corners that may cause scratches or
workers. Cages should be designed and arranged in animal
so that the risk of workers being accidentally grabbed or
minimized. Access to areas where macaques are maintained and
should be limited either to workers who are properly trained in
procedures to avoid risk of infection or to those accompanied
The routine screening of macaques for evidence of B virus
not recommended. Even animals previously found to be negative
or antibody might be positive at the time of a human exposure.
screening may increase the risk of infection to workers. In
in which laboratory studies may cause immunosuppression of the
the investigator may elect to determine the infection status of
animals to be used, since virus shedding might be enhanced
circumstances. Macaques with oral lesions suggestive of active
infection should be quarantined until the lesions have healed
the risk of virus transmission to workers and other macaques.
Persons who handle macaques, including primate veterinarians
scientific investigators, should be trained in proper methods
restraint and in the use of protective clothing to help prevent
and scratches. Such persons should be acquainted with standard
operating procedures and other available training materials
handling animals. Training should be followed up with continual
observation for lapses in these procedures as they occur.
handlers should also be educated concerning the nature of B
infection; the need to prevent bites, scratches, and other
macaque secretions; and the need to clean wounds immediately.
should be educated concerning the early symptoms of B virus
and the need to report injuries and/or symptoms suggestive of B
infection to supervisors immediately. Animal handlers should be
that persons who are immunosuppressed because of medication or
underlying medical conditions may be at higher risk for B virus
infection. A pre-employment serum sample should be obtained
persons who work with macaques, and additional samples should
obtained annually to serve as a baseline for retrospective
the event of a suspected B virus infection. Such specimens
aliquoted and frozen, preferably at -70 C.
All bite or scratch wounds incurred from macaques or from cages
might be contaminated with macaque secretions and that result
bleeding should be immediately and thoroughly scrubbed and
with soap and water. Such incidents should be reported to the
animal-care supervisor and recorded in a bite/scratch log.
wounds that can be adequately cleansed probably require no
treatment. More extensive wounds should be referred to a
consultant. Each animal-care facility should identify a medical
consultant who will be on call to assist in such situations.
consultants, in addition to having general knowledge concerning
bites, should be knowledgeable concerning the hazard of B virus
infection, its symptoms, and treatment. Following a bite or
the animal handler should be instructed to report immediately
lesions or neurologic symptoms (such as itching, pain, or
near the site of the wound or any other unusual illness. It is
responsibility of the supervisor, when no illness is reported,
determine the clinical status of the handler at weekly
intervals for 1
month after the exposure. Symptoms suggestive of B virus
should be reported immediately to the medical consultant. When
possibility of B virus illness is seriously entertained,
diagnostic studies should be performed and specific antiviral
should be instituted. (At the time of this writing,
limited clinical data indicate acyclovir to be the drug of
physician may wish to consult the Viral Exanthems and
Branch, Division of Viral Diseases, CDC (Dr. Gary Holmes,
((404))329-1338) and, for laboratory assistance, the Southwest
Foundation for Biomedical Research (Dr. Julia Hilliard,
In some situations, prophylactic treatment with an antiviral
be considered in the absence of signs or symptoms suggestive of
infection. Such a situation might arise when an animal handler
a deep, penetrating wound that cannot be adequately cleansed.
situations, studies to determine the B virus status of the
should be considered, especially if the animal has clinical
suggestive of B virus infection. These situations should be
the medical consultant, who may wish to consult the resource
mentioned above. There is no evidence that pooled immune
effective in preventing or ameliorating B virus infection.
hyperimmune human B virus globulin nor vaccine against B virus
Reported by The B Virus Working Group: JE Kaplan, MD (Coordinator),
Whitley, MD, University of Alabama--Birmingham, Birmingham,
Swenson, DVM, Southeast Regional Primate Center, Atlanta, Georgia.
Cole, US Army Medical Research Institute of Infectious Diseases,
Detrick, Maryland. DO Johnsen, DVM, RW McKinney, PhD, RA Whitney,
National Institutes of Health, Bethesda, Maryland. JH Vickers, DVM,
Food and Drug Administration, Bethesda, Maryland. M Balk, DVM, MS,
River Laboratories, Wilmington, Massachusetts. MD Daniel, DVM, PhD,
England Regional Primate Center, Southboro, Massachusetts. B Brock,
Lederle Laboratories, Pearl River, New York. T Butler, DVM, MS, J
PhD, Southwest Foundation for Biomedical Research, San Antonio,
Glosser, DVM, US Dept of Agriculture, Washington, DC. JR Broderson,
PhD, GP Holmes, MD, JW McVicar, DVM, CDC.
Sabin AB, Wright AM. Acute ascending myelitis following a
with the isolation of a virus capable of reproducing the
disease. J Exp
Palmer AE. B virus, Herpesvirus simiae: historical perspective.
CDC. Herpes B encephalitis--California. MMWR 1973;22:333-4.
Stones PB. Cited in: Graham-Jones O, ed. Some diseases of
communicable to man in Britain. London: Pergamon Press,
CDC. B-virus infection in humans--Pensacola, Florida. MMWR
Fox JG, Newcomer CE, Rozmiarek H. Selected zoonoses and other
hazards. In: Fox JG, Cohen BJ, Loew FM, eds. Laboratory animal
medicine. Orlando, Florida: Academic Press, 1984;619-20.
Whitney RA, Johnson DJ, Cole WC. The subhuman primate: a guide
veterinarian. Edgewood Arsenal, Maryland: Department of the
Edgewood Arsenal Medical Research Laboratory, 1967; Edgewood
special publication no. (EASP)100-26.
Boulter EA, Thornton B, Bauer DJ, Bye A. Successful treatment
experimental B virus (Herpesvirus simiae) infection with
Med J 1980;280:681-3.
CDC, National Institutes of Health. Biosafety in
biomedical laboratories. Bethesda: US Department of Health and
Services, Public Health Service, 1984:63; DHHS publication no.
(CDC)84-8395. (Reprinted July 1986.)
Cabasso VJ, Chappell WA, Avampato JE, Bittle JL. Correlation of
and herpes simplex virus antibodies in human sera. J Lab Clin
Van Hoosier GL Jr, Melnick JL. Neutralizing antibodies in human
Herpesvirus simiae. Texas Rep Biol Med 1961;19:376-80.
*In his review, Palmer (2) reports a total of 24 cases from 1932 to
citing a reference from CDC (3). Documentation of B virus
however, was established in only 17 of these cases; an 18th case,
occurred in 1958 (4), was omitted in Palmer's review.
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