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Lymphocytic Choriomeningitis
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What
is lymphocytic choriomeningitis? |
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Lymphocytic choriomeningitis,
or LCM, is a rodent-borne viral infectious disease that presents as aseptic
meningitis (inflammation of the membrane, or meninges, that surrounds
the brain and spinal cord), encephalitis (inflammation of the brain),
or meningoencephalitis (inflammation of both the brain and meninges).
Its causative agent is the lymphocytic choriomeningitis virus (LCMV),
a member of the family Arenaviridae, that was initially isolated in 1933.
Although LCMV is most commonly recognized as causing neurological disease,
as its name implies, asymptomatic infection or mild febrile illnesses
are common clinical manifestations. Additionally, pregnancy-related infection
has been associated with abortion, congenital hydrocephalus and chorioretinitis,
and mental retardation.
Where
is the disease found? |
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LCM and milder LCMV
infections have been reported in Europe, the Americas, Australia, and
Japan, and may occur wherever infected rodent hosts of the virus are found.
However, the disease has historically been underreported, often making
it difficult to determine incidence rates or estimates of prevalence by
geographic region. Several serologic studies conducted in urban areas
have shown that the prevalence of LCMV infection among humans ranges from
2% to 10%.
How
is LCMV spread, and how do humans become infected? |
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LCMV is naturally
spread by the common house mouse, Mus musculus. Once infected,
these mice can become chronically infected by maintaining virus in their
blood and/or persistently shedding virus in their urine, a common characteristic
of other arenavirus infections in rodents. Chronically infected female
mice usually transmit infection to their offspring, which in turn become
chronically infected.
Humans become infected
by inhaling infectious aerosolized particles of rodent urine, feces, or
saliva, by ingesting food contaminated with virus, by contamination of
mucus membranes with infected body fluids, or by directly exposing cuts
or other open wounds to virus-infected blood. LCMV infection has also
been documented among staff handling infected hamsters. Person-to-person
transmission has not been reported, with the exception of vertical transmission
from an infected mother to fetus.
What
are the symptoms of LCM? |
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The incubation period
of LCMV infection is usually between 8 and 13 days. A characteristic biphasic
febrile illness then follows. The initial phase, which may last as long
as a week, typically begins with any or all of the following symptoms: fever,
malaise, anorexia, muscle aches, headache, nausea, and vomiting. Other symptoms
that appear less frequently include sore throat, cough, joint pain, chest
pain, testicular pain, and parotid (salivary gland) pain. Following a few
days of remission, the second phase of the disease occurs, consisting of
symptoms of meningitis (for example, fever, headache, and a stiff neck)
or characteristics of encephalitis (for example, drowsiness, confusion,
sensory disturbances, and/or motor abnormalities, such as paralysis). LCMV
has also been known to cause acute hydrocephalus, which often requires surgical
shunting to relieve increased intracranial pressure. In rare instances,
infection results in myelitis (inflammation of the spinal cord) and presents
with symptoms such as muscle weakness, paralysis, or changes in body sensation.
An association between LCMV infection and myocarditis (inflammation of the
heart muscles) has been suggested.
During the first
phase of the disease, the most common laboratory abnormalities are a low
white blood cell count (leukopenia) and a low platelet count (thrombocytopenia).
Liver enzymes in the serum may also be mildly elevated. After the onset
of neurological disease during the second phase, an increase in protein
levels, an increase in the number of white blood cells or a decrease in
the glucose levels in the cerebrospinal fluid (CSF) is usually found.
Are
there any complications after recovery? |
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Previous observations
have shown that most patients who develop aseptic meningitis or encephalitis
due to LCMV recover completely. No chronic infection has been described
in humans, and after the acute phase the virus is cleared. However, as
in all infections of the central nervous system, particularly encephalitis,
temporary or permanent neurological damage is possible. Nerve deafness
and arthritis have been reported. Infection of the human fetus during
the early states of pregnancy may lead to developmental deficits that
are permanent.
Is
the disease ever fatal? |
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LCM is usually not
fatal. In general, mortality is less than 1%.
How
is LCM treated? |
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Aseptic meningitis,
encephalitis, or meningoencephalitis requires hospitalization and supportive
treatment based on severity. There is no specific drug therapy for LCM.
Anti-inflammatory drugs, such as corticosteroids, may be considered under
specific circumstances. Although studies have shown that ribavirin, a
drug used to treat several other viral diseases, is effective against
LCMV in vitro, there is no established evidence to support its use for
treatment of LCM in humans.
Who
is at risk for LCMV infection? |
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Individuals of all
ages who come into contact with urine, feces, saliva, or blood of the
house mouse are potentially at risk for infection. Laboratory workers
who themselves handle infected animals are also at risk. However, this
risk can be minimized by utilizing animals from sources that regularly
test for the virus, wearing proper protective laboratory gear, and following
appropriate safety precautions. Owners of pet mice or hamsters may be
at risk for infection if these animals originate from colonies with circulating
LCMV, or if the animals become infected from other wild mice. Human fetuses
are at risk of acquiring infection vertically from infected maternal blood.
How
can LCMV infections be prevented? |
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Like many other rodent-borne
infectious diseases, LCMV infection can be prevented by avoiding or minimizing
direct physical contact with rodents or exposure to their excreta. Adequate
ventilation should be provided to any heavily infested, previously unventilated
enclosed room or dwelling prior to cleanup. A liquid disinfectant, such
as a diluted household bleach solution, should be applied to visible rodent
droppings and their immediate surroundings. Gloves should be worn when
disinfecting and cleaning up rodent excreta. Rodent spring traps may be
set up in households or dwellings where rodent infestations are a concern.
What
needs to be done to address the threat of LCMV? |
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The geographic distributions
of the rodent hosts are widespread both domestically and abroad. However,
infrequent recognition and diagnosis, and therefore underreporting, of
LCM, have limited scientists’ ability to estimate incidence rates and
prevalence of disease among humans. Understanding the epidemiology of
LCM and LCMV infections will help to further delineate risk factors for
infection and develop effective preventive strategies. Increasing physician
awareness will improve disease recognition and reporting, which may lead
to better characterization of the natural history and the underlying immunopathological
mechanisms of disease, and stimulate future therapeutic research and development.
Suggested
Reading |
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Jahrling PB, Peters
CJ. Lymphocytic choriomeningitis virus: a neglected pathogen of man. Arch
Pathol Lab Med 1992;116:486-8.
Peters CJ, Buchmeier
M, Rollin PE, Ksiazek TG. Arenaviruses. In: Belshe RB, ed. Textbook of
Human Virology. 2nd ed. St. Louis: Mosby-Year Book, Inc. 1991:541-70.
Peters CJ, et al.
Arenaviridae: Biology of viruses. In: Fields BN, Knipe DM, Howley PM,
et al, eds. Fields Virology. 3rd ed. Philadelphia: Lippincott-Raven Publishers.
1996:1527-51.
Peters CJ. Arenaviruses.
In: Richman DD, Whitley RJ, Hayden FG, eds. Clinical Virology.
New York: Churchill
Livingstone, Inc. 1997: 973-96.
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