How to recognize and treat lymphocytic choriomeningitis lcm

LCMV is most commonly recognized as causing neurological disease, as its name implies, though infection without symptoms or mild febrile illnesses are more common clinical manifestations.

For infected persons who do become ill, onset of symptoms usually occurs 8-13 days after exposure to the virus as part of a biphasic febrile illness. This initial phase, which may last as long as a week, typically begins with any or all of the following symptoms: fever, malaise, lack of appetite, muscle aches, headache, nausea, and vomiting. Other symptoms appearing less frequently include sore throat, cough, joint pain, chest pain, testicular pain, and parotid (salivary gland) pain.

Following a few days of recovery, a second phase of illness may occur. Symptoms may consist of meningitis (fever, headache, stiff neck, etc.), encephalitis (drowsiness, confusion, sensory disturbances, and/or motor abnormalities, such as paralysis), or meningoencephalitis (inflammation of both the brain and meninges). LCMV has also been known to cause acute hydrocephalus (increased fluid on the brain), 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.

Previous observations show that most patients who develop aseptic meningitis or encephalitis due to LCMV survive. No chronic infection has been described in humans, and after the acute phase of illness, the virus is cleared from the body. 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.

Women who become infected with LCMV during pregnancy may pass the infection on to the fetus. Infections occurring during the first trimester may result in fetal death and pregnancy termination, while in the second and third trimesters, birth defects can develop. Infants infected In utero can have many serious and permanent birth defects, including vision problems, mental retardation, and hydrocephaly (water on the brain). Pregnant women may recall a flu-like illness during pregnancy, or may not recall any illness.

LCM is usually not fatal. In general, mortality is less than 1%.

LCMV infection can be prevented by avoiding contact with wild mice and taking precautions when handling pet rodents (i.e. mice, hamsters, or guinea pigs).

Rarely, pet rodents may become infected with LCMV from wild rodents. Breeders, pet stores, and pet owners should take measures to prevent infestations of wild rodents. Pet rodents should not come into contact with wild rodents. If you have a pet rodent, wash your hands with soap and water (or waterless alcohol-based hand rubs when soap is not available and hands are not visibly soiled) after handling rodents or their cages and bedding.

If you have a rodent infestation in and around your home, take the following precautions to reduce the risk of LCMV infection:

  • Seal up rodent entry holes or gaps with steel wool, lath metal, or caulk.
  • Trap rats and mice by using an appropriate snap trap.
  • Clean up rodent food sources and nesting sites and take precautions when cleaning rodent-infected areas:
    • Use cross-ventilation when entering a previously unventilated enclosed room or dwelling prior to cleanup.
    • Put on rubber, latex, vinyl or nitrile gloves.
    • Do not stir up dust by vacuuming, sweeping, or any other means.
    • Thoroughly wet contaminated areas with a bleach solution or household disinfectant.
    • Hypochlorite (bleach) solution: Mix 1 and 1/2 cups of household bleach in 1 gallon of water.
    • Once everything is wet, take up contaminated materials with damp towel and then mop or sponge the area with bleach solution or household disinfectant.
    • Spray dead rodents with disinfectant and then double-bag along with all cleaning materials and throw bag out in an appropriate waste disposal system.
    • Remove the gloves and thoroughly wash your hands with soap and water (or waterless alcohol-based hand rubs when soap is not available and hands are not visibly soiled).

The geographic distributions of the rodent hosts are widespread both domestically and abroad. However, infrequent recognition and diagnosis, and historic 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.

, PhD, University of Wisconsin-Madison

Most people become infected when they inhale dust or eat food contaminated with the urine, feces, or another body fluid of an infected mouse or hamster.

Most people with lymphocytic choriomeningitis have no or mild symptoms, but some have a flu-like illness, and a few develop meningitis or a brain infection.

To diagnose lymphocytic choriomeningitis, doctors do a spinal tap and blood tests to check for the virus.

Treatment aims to relieve symptoms, but if people have meningitis or a brain infection, they are hospitalized and may be given an antiviral drug.

Lymphocytic choriomeningitis virus is caused by an arenavirus and is spread by rodents. Usually, people become infected when they inhale dust or eat food contaminated with the urine, feces, or another body fluid of an infected hamster or gray house mouse. When lymphocytic choriomeningitis is transmitted by mice, it occurs mainly in adults during the autumn and winter.

Symptoms

Most people with lymphocytic choriomeningitis have no or mild symptoms.

Symptoms, if they occur, develop about 1 to 2 weeks after people are infected.

Some people have a flu-like illness, with fever, chills, a general feeling of illness (malaise), weakness, muscle aches (especially in the lower back), and pain behind the eyes. People may be sensitive to light, lose their appetite, and feel nauseated or light-headed. Sore throat occurs less often.

After 5 days to 3 weeks, people usually improve for 1 or 2 days. Many of them then worsen. Fever and headache return, and a rash may appear. The joints of the fingers and hands may swell. Infection may spread to the salivary glands (causing mumps) and to the testes.

In a few people, the tissues that cover the brain and spinal cord (meninges) become infected (called meningitis). Meningitis typically causes a stiff neck that makes lowering the chin to the chest difficult or impossible. Very few people develop a brain infection (encephalitis), which may cause paralysis, problems with movement, or other symptoms of brain dysfunction.

If pregnant women become infected, the fetus may have problems, such as hydrocephalus (accumulation of excess fluid within the brain or meninges), chorioretinitis (an eye infection), and intellectual disability. Chorioretinitis can cause blurred vision, eye pain, sensitivity to light, and blindness. If pregnant women are infected during the 1st trimester, the fetus may die.

, PhD, University of Wisconsin-Madison

Lymphocytic choriomeningitis virus is endemic in rodents. Human infection results most commonly from exposure to dust or food contaminated by the gray house mouse or hamsters, which harbor the virus and excrete it in urine, feces, semen, and nasal secretions. The percentage of infected house mice in a population may vary by geographic location; it is estimated that 5% of house mice throughout the US carry lymphocytic choriomeningitis virus and can transmit the virus throughout their life without showing any sign of illness. When transmitted by mice, the disease occurs primarily in adults during autumn and winter.

Symptoms and Signs

The incubation period for lymphocytic choriomeningitis is 1 to 2 weeks.

Most patients have no or minimal symptoms. Some develop a flu-like illness. Fever, usually 38.5 to 40 ° C, with rigors is accompanied by malaise, weakness, myalgia (especially lumbar), retro-orbital headache, photophobia, anorexia, nausea, and light-headedness. Sore throat and dysesthesia occur less often.

After 5 days to 3 weeks, patients may improve for 1 or 2 days. Many relapse with recurrent fever, headache, rashes, swelling of metacarpophalangeal and proximal interphalangeal joints, meningeal signs, orchitis, parotitis, or alopecia of the scalp.

Aseptic meningitis occurs in a minority of patients. Rarely, frank encephalitis, ascending paralysis, bulbar paralysis, transverse myelitis, or other neurologic symptoms can occur. Neurologic sequelae are rare in patients with meningitis but occur in up to 33% of patients with encephalitis.

Infection during pregnancy may cause fetal abnormalities, including hydrocephalus, chorioretinitis, and intellectual disability. Infections that occur during the 1st trimester may result in fetal death.

Diagnosis

Polymerase chain reaction (PCR), cerebrospinal fluid analysis, antibody detection, and viral culture

Lymphocytic choriomeningitis is suspected in patients with exposure to rodents and an acute illness, particularly aseptic meningitis or encephalitis. Aseptic meningitis may lower cerebrospinal fluid glucose mildly but occasionally to as low as 15 mg/dL (0.83 mmol/L). Cerebrospinal fluid white blood cell counts range from a few hundred to a few thousand cells, usually with > 80% lymphocytes. White blood cell counts of 2000 to 3000/mcL (2 to 3 x 10 9 /L) and platelet counts of 50,000 to 100,000/mcL (50 to 100 x 10 9 /L) typically occur during the first week of illness.

Diagnosis can be made by

PCR or by isolation of the virus from the blood or cerebrospinal fluid during the acute stage of illness

Indirect immunofluorescence assays of inoculated cell cultures, although these tests are most likely to be used in research laboratories

Tests that detect seroconversion of antibody to the virus

Treatment

Treatment of lymphocytic choriomeningitis is supportive. Measures needed depend on the severity of the illness. If aseptic meningitis, encephalitis, or meningoencephalitis develops, patients should be hospitalized, and treatment with ribavirin can be considered.

Anti-inflammatory drugs (eg, corticosteroids) may be considered in certain circumstances.

Key Points

In humans, lymphocytic choriomeningitis is usually acquired via exposure to dust or consumption of food contaminated by mouse or hamster excreta.

Most patients have no or minimal symptoms, but some develop a flu-like illness, and a few develop aseptic meningitis.

Infection during pregnancy may cause fetal abnormalities; if infection occurs during the 1st trimester, the fetus may die.

Abstract

The hypothesis that treatment with antilymphocytic serum (ALS) can provoke latent virus infections has been investigated. In adult mice infections with sublethal doses of LCM virus usually result in the development of immunity to the virus and at the same time to a prolonged latent infection. In the experiments described an intensive treatment with large doses of ALS was given to mice which had recovered from LCM virus infection. At the beginning of the treatment the mice had high titers of complement-fixing antibodies in their blood and no detectable virus. The data presented show that in spite of the immunity the ALS treatment provoked the occult virus and led to the development of viremia in all the treated mice. In some, very high virus titers were demonstrable. When the ALS treatment was discontinued the viremia disappeard again. In most of the mice the ALS did not suppress the complement-fixing antibody titers and in some there was even a considerable increase in titer. In such cases the increases in virus titers and in antibody titers were closely related to one another. These results demonstrate once again that the complement-fixing antibodies to the LCM virus in mice probably do not influence the virus.

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Selected References

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Abstract

The arenavirus, lymphocytic choriomeningitis virus (LCMV) has a single-stranded RNA genome composed of a large (L) and a small (S) RNA segment. The completed sequence of LCMV, presented here, reveals a formerly unknown gene (Z) on the L genomic segment. This gene is encoded in the positive or message-sense of the viral genomic RNA, whereas the adjacent gene (L) is in the genome-complementary, or negative sense. The ambisense polarity of the genes on the L RNA reiterates the polarity of genes on the small (S) genomic segment. The Z gene encodes a 10-kDa protein containing a single zinc-finger sequence (Cys2His2). A small RNA representing the message sense of the Z gene is found in infected cells and within virions. In contrast to the known LCMV proteins having structural or enzymatic functions, the predicted Z gene product is most likely to be an RNA-binding protein with a regulatory role. The encapsidation of a message sense Z RNA suggests a role for this gene immediately following virus penetration. The U/Z intergenic region is rich in cytidylic acid (C) and presents an unusual RNA structure. All cDNA clones of the intergenic region differ from each other within a certain poly(C) stretch and lack a 30-base region present in the direct RNA sequence. Finally, the completed sequence establishes that the L RNA Fend is complementary to its 3′ end. The L RNA termini, similarto the S RNAtermini, have a small but potentially important asymmetry of sequence. LCMV is the first arenavirus to be completely sequenced.

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When most people hear the term rodent-borne disease, the likes of Hantavirus, plague, rat-bite fever and salmonellosis are probably the first few to come to mind. However, there’s another rodent-borne viral infectious disease people should be aware of as we enter the winter season — Lymphocytic choriomeningitis, or LCM, which is caused by lymphocytic choriomeningitis virus (LCMV). LCVM is transmitted to humans following exposure to fresh urine, droppings, saliva, or nesting materials from infected house mice. Individuals who are bit by an infected rodent may also be at risk of exposure.

How to recognize and treat lymphocytic choriomeningitis lcm

The Centers for Disease Control and Prevention (CDC) estimates that 5 percent of house mice throughout the United States carry LCMV and are able to transmit the virus. Infections are more common in the colder months when mice enter homes seeking shelter from the looming winter elements.

Symptoms and Treatment of LCMV

Most commonly, infection with LCMV has two phases. The first phase has non-specific “flu-like” symptoms, such as fever, malaise, lack of appetite, muscle aches, headache, nausea, and vomiting. The second phase of illness is dominated by neurologic disease. According to the CDC, symptoms may include meningitis (fever, headache, stiff neck, etc.), encephalitis (drowsiness, confusion, sensory disturbances and/or motor abnormalities), or meningoencephalitis (inflammation of both the brain and meninges). Most cases are self-limited, but others may require hospitalization based on severity. That said, infection is a much greater problem for women who become infected with LCMV during pregnancy because they may pass the infection on to the fetus with serious consequences.

How to Prevent LCMV

LCMV infection can be prevented by avoiding contact with mice and mouse excrement. Homeowners should seal up rodent entry holes or gaps with a silicone-based caulk, steel wool, or a combination of both. It’s also important to take precautions when handling pet rodents (i.e. mice, hamsters, or guinea pigs). For more information on preventing a rodent infestation, click here.

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Medical Care

No antiviral agents have undergone clinical trials for the treatment of lymphocytic choriomeningitis virus (LCMV) infection.

Early diagnosis and supportive care (eg, fluid replacement, NSAID therapy) are essential, particularly in immunocompromised patients. Reduce immunosuppression, when feasible.

No specific drug treatment is indicated in most cases of LCMV infection. Most patients improve spontaneously within 1-3 weeks with no sequelae.

Ribavirin has in vitro activity against LCMV and has been used with success in transplant recipients with severe disease. Intravenous ribavirin is not commercially available. Oral ribavirin is dosed based on ideal body weight and renal function. Patients should be monitored carefully for potential toxicity, including hemolytic anemia, while receiving ribavirin. [20, 14]

Favipiravir (T-705), a selective inhibitor of RNA-dependent RNA polymerase (RdRp), has been shown to inhibit LCMV in vitro. It has also demonstrated promising efficacy at reducing mortality of other arenavirus infections in animal models. Further study is needed to ascertain if favipiravir could be safely used to treat infections with arenaviruses, including LCMV in humans. [21, 22]

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