Lymphocytic choriomeningitis (LCM) is a viral disease caused by the lymphocytic choriomeningitis virus (LCMV). The virus mainly infects rodents, especially the common house mouse (Mus musculus), and can spread to humans through contact with infected rodents or their waste. The illness can range from mild, flu-like symptoms to more serious brain and nervous system problems, such as meningitis (inflammation of the membranes covering the brain and spinal cord) or encephalitis (inflammation of the brain itself).
In the early stage of infection, symptoms are often mild and may include fever, headache, tiredness, muscle pain, nausea, vomiting, and loss of appetite. Many people recover without realizing they were infected. However, some may develop a second, more serious phase affecting the nervous system. This can cause symptoms such as a stiff neck, sensitivity to light, confusion, or difficulty with movement. People with weakened immune systems are at higher risk of severe illness. Infection during pregnancy is especially dangerous because the virus can pass from mother to baby, possibly leading to miscarriage, birth defects, or stillbirth.
Humans usually become infected by breathing in dust or eating food contaminated with the saliva, urine, or droppings of infected rodents. The virus can also spread from an infected mother to her unborn child, or rarely, through organ transplants. It does not spread from person to person through normal contact.
There is no specific medicine to cure LCM, so treatment focuses on easing symptoms. People with severe cases, especially those involving meningitis or encephalitis, may need hospital care.
The best way to prevent LCM is to avoid contact with rodents and their droppings. This includes sealing holes and cracks where mice could enter homes, cleaning rodent-contaminated areas carefully while wearing gloves and a mask, and handling pet rodents like hamsters and guinea pigs with care. There is currently no vaccine to protect against LCMV.
Signs and Symptoms
Infection with the lymphocytic choriomeningitis virus (LCMV) produces a broad spectrum of symptoms that depend on the stage of illness, the person’s immune status, and the amount of virus involved in the exposure. The disease typically follows a biphasic (two-phase) course, beginning with mild, flu-like symptoms and, in some cases, progressing to more serious neurological involvement.
Symptoms in Humans
Early symptoms of lymphocytic choriomeningitis usually appear after a short incubation period and are often nonspecific. They may include fever, headache, muscle aches (myalgia), nausea, vomiting, and loss of appetite. These symptoms reflect the body’s initial immune response to viral infection. Many people experience only mild illness or may not notice any symptoms at all. However, in others, especially those with higher exposure or weaker immune defenses, the disease can progress to a second stage marked by inflammation of the membranes surrounding the brain and spinal cord.
When the central nervous system becomes involved, patients may develop meningitis or meningoencephalitis (a combination of meningitis and encephalitis). These conditions are characterized by more severe signs, such as neck stiffness, sensitivity to light (photophobia), confusion, drowsiness, and difficulty concentrating. In some rare but serious cases, neurological complications can advance to seizures, paralysis, or coma. Individuals with compromised immune systems, such as organ transplant recipients or those with chronic illnesses, face an increased risk of prolonged or fatal infection.
Stages of Infection
The course of LCMV infection generally occurs in two distinct phases.
- First phase (systemic phase): This phase lasts about five to seven days and is marked by nonspecific, flu-like symptoms such as fever, fatigue, headache, and muscle pain. Some patients also experience nausea or abdominal discomfort. At this point, the virus is circulating in the bloodstream, triggering the immune system’s initial response. This phase may resolve spontaneously, leading to complete recovery in mild cases.
- Second phase (neurological phase): In some individuals, after a brief period of apparent improvement, symptoms return and intensify. This phase signals the virus’s entry into the central nervous system. Patients may experience recurrent fever, stiff neck, confusion, photophobia, or balance disturbances. Meningitis (inflammation of the protective layers surrounding the brain and spinal cord) and encephalitis (inflammation of brain tissue) are the hallmark complications of this stage. Recovery from the neurological phase can take several weeks, and some patients may experience lingering effects such as fatigue, headaches, or cognitive difficulties.
Incubation Period
The incubation period, the time between exposure to the virus and the onset of symptoms, typically ranges from 8 to 13 days, though it can vary depending on factors such as the amount of virus encountered and the individual’s immune response. During this period, the virus multiplies silently in the body, without causing noticeable symptoms. Like other arenaviruses, LCMV begins replicating in tissues before spreading through the bloodstream, eventually reaching the central nervous system in some cases.
Most human infections occur after exposure to environments contaminated with the urine, saliva, or droppings of infected rodents, particularly the common house mouse (Mus musculus). People exposed to higher viral doses, for instance, when cleaning heavily infested areas, may experience shorter incubation times and more intense symptoms.
Causes and Transmission
Lymphocytic choriomeningitis (LCM) results from infection by a specific virus and involves particular animal hosts. The virus spreads through distinct routes, including direct and indirect contact, which govern the transmission risk.
Etiology and the LCM Virus
The lymphocytic choriomeningitis virus (LCMV) belongs to the Arenaviridae family, a group of viruses known to infect rodents and occasionally humans. LCMV is an enveloped, single-stranded RNA virus composed of two distinct RNA segments, one encoding structural proteins and the other coding for enzymes needed for viral replication. This segmented structure allows the virus to efficiently adapt and persist in its rodent hosts.
In humans, the virus typically enters the body through the respiratory tract, mucous membranes (such as the eyes, mouth, or nose), or small skin abrasions. Once inside, it can multiply in various tissues and, in severe cases, cross the blood-brain barrier, the protective layer separating the brain from the bloodstream. When this occurs, LCMV causes inflammation of the brain and surrounding membranes, leading to neurological complications such as meningitis or encephalitis.
LCMV is resilient in environments contaminated with rodent excretions, especially in cool and humid conditions. The virus can remain infectious for several days in dried urine, feces, or nesting materials, which allows for indirect transmission to humans. Despite this environmental stability, LCMV is not easily spread between people, and human-to-human transmission does not occur through casual contact, coughing, or sneezing.
Reservoir Hosts
The primary natural reservoir of LCMV is the common house mouse (Mus musculus), which carries the virus without showing signs of illness. Once infected, mice remain lifelong carriers, shedding the virus continuously in their urine, feces, saliva, and nesting materials. This persistent shedding enables the virus to remain active in mouse populations and their environments for extended periods.
While the house mouse is the main source of infection, other rodents can also act as secondary reservoirs. Pet rodents such as hamsters, guinea pigs, and fancy mice have occasionally been implicated in human outbreaks, particularly in households or laboratory settings. Wild rodents, including voles and rats, may also harbor the virus in certain geographic regions, though less frequently.
The close relationship between rodents and human environments increases the risk of exposure. Infestations in homes, food storage areas, or laboratories can significantly elevate infection risk. Even brief or indirect contact such as inhaling dust contaminated with rodent droppings can be enough to transmit the virus.
Modes of Transmission
LCMV spreads to humans primarily through indirect exposure to contaminated materials rather than direct contact with infected animals. The most common routes of infection include:
- Inhalation of aerosolized particles: When rodent urine or droppings dry and become airborne as dust, humans can inhale viral particles, leading to infection.
- Direct contact: Touching contaminated surfaces, nesting materials, or infected rodents, especially when skin cuts or abrasions are present, can allow the virus to enter the body.
- Ingestion: Eating food contaminated with rodent droppings or saliva can serve as another, though less common, route of infection.
LCMV can also be transmitted through less common but significant pathways:
- Vertical transmission (mother-to-fetus): If a pregnant woman becomes infected, the virus can cross the placenta and infect the unborn baby, potentially causing miscarriage, birth defects, or fetal death.
- Organ transplantation: In rare cases, the virus has been transmitted through infected donor organs or tissues, leading to severe illness in recipients, especially those with suppressed immune systems.
Person-to-person transmission of LCMV is extremely rare and has only been documented in cases involving organ or tissue transplantation or congenital infection. Routine social contact, including touching or sharing household items, does not spread the virus.
Certain environments and occupations carry a higher risk of LCMV exposure. People who live or work in rodent-infested buildings, such as farms, storage facilities, or laboratories handling rodents, are at increased risk. Laboratory personnel working with infected rodents or their tissues without adequate biosafety precautions face particular danger of accidental infection.
Households with pet rodents, especially hamsters or mice obtained from breeding colonies or pet stores with LCMV circulation, also present a potential risk. Pregnant women are advised to avoid handling rodents or cleaning cages, as even minimal exposure to contaminated bedding or droppings could result in fetal infection.
Diagnosis of Lymphocytic Choriomeningitis
Because the early phase of infection often mimics common viral illnesses, accurate diagnosis requires careful clinical judgment and appropriate laboratory confirmation.
Clinical Evaluation
The clinical assessment begins with the observation of characteristic symptoms such as fever, headache, muscle aches, nausea, vomiting, and stiff neck—typical signs of meningeal irritation. Physicians often look for a biphasic illness pattern, where an initial flu-like phase is followed by a neurological phase involving meningitis or encephalitis. This temporal progression, usually occurring 15 to 21 days after infection, helps distinguish LCM from other viral infections.
A detailed neurological examination is essential to identify involvement of the central nervous system (CNS). Findings such as confusion, sensitivity to light (photophobia), seizures, or focal neurological deficits (localized weakness or paralysis) indicate progression to the second phase of illness and warrant immediate further testing. Clinical suspicion increases when such symptoms occur in individuals with a documented history of rodent exposure, particularly laboratory workers, pet owners, or people living in rodent-infested environments.
Laboratory Testing
Definitive diagnosis depends on serological and molecular testing to confirm infection with lymphocytic choriomeningitis virus (LCMV). The detection of LCMV-specific IgM antibodies in the blood or cerebrospinal fluid (CSF) indicates a recent or active infection, while the presence of IgG antibodies suggests past exposure. These antibodies are usually identified using techniques such as enzyme-linked immunosorbent assay (ELISA) or immunofluorescent antibody (IFA) testing.
For direct viral detection, polymerase chain reaction (PCR) and its advanced form, reverse transcription PCR (RT-PCR), are used to identify viral RNA. These molecular methods are especially valuable during the early stages of illness when antibodies may not yet be detectable. In suspected congenital infections, where the virus is transmitted from mother to fetus, PCR may be applied for prenatal diagnosis, although its sensitivity can vary depending on viral load and the stage of pregnancy.
CSF analysis in LCM cases typically reveals lymphocytic pleocytosis (an increased number of lymphocytes), slightly elevated protein levels, and normal glucose concentrations, findings consistent with viral meningitis. However, these results are not unique to LCMV, so laboratory confirmation through antibody or PCR testing remains essential. Combining serology and PCR significantly improves diagnostic accuracy, especially in early or atypical cases.
Historically, complement-fixation tests were used to detect LCMV, but these have largely been abandoned due to poor sensitivity and specificity. Because the virus is not always detectable in blood or CSF, particularly in late or congenital infections, laboratory testing can yield false negatives, suggesting that LCMV infections may be more common than currently recognized.
Differential Diagnosis
Lymphocytic choriomeningitis must be differentiated from other viral meningitis causes, such as enteroviruses, herpes simplex virus, and West Nile virus. The absence of rodent exposure and differences in symptom progression can help distinguish these infections from LCMV.
Bacterial meningitis must also be ruled out through CSF cultures and clinical presentation, as it typically shows more severe symptoms and lower glucose levels in the CSF. In regions where tuberculosis meningitis or autoimmune encephalitis are prevalent, these conditions should be considered based on clinical findings, geographic factors, and patient history.
Differentiating LCMV infection from other central nervous system (CNS) disorders is vital because management strategies differ significantly. Correct diagnosis prevents unnecessary antibiotic use.
Prevention and Control Measures
Studies emphasize that effective control of rodent populations remains the cornerstone of preventing LCMV transmission, as rodents particularly the common house mouse (Mus musculus) serve as the primary reservoirs of the virus. Preventive measures begin with rodent-proofing residential and commercial spaces by sealing potential entry points such as cracks, gaps around doors, vents, and utility lines. The Centers for Disease Control and Prevention (CDC) recommends regular structural inspections to identify and block rodent access routes, alongside the use of traps in areas showing signs of activity, including kitchens, pantries, and waste disposal zones. Handling of traps or rodent-contaminated materials should always be done using gloves and masks to minimize exposure to aerosolized viral particles. Maintaining environmental hygiene is equally essential; food should be secured in rodent-proof containers, garbage must be tightly sealed and removed frequently, and outdoor clutter such as woodpiles or dense vegetation should be eliminated to discourage nesting. Individuals whose occupations entail high exposure risks such as pest control operators, laboratory technicians, or animal caretakers are advised to wear protective clothing and respiratory gear during work. Furthermore, public health authorities strongly advise pregnant women to avoid environments with known rodent infestations, as congenital LCMV infection carries a significant risk of severe neurological damage to the fetus.
Treatment and Management
Supportive care is the foundation of treatment for lymphocytic choriomeningitis virus (LCMV) infection, as no specific antiviral therapy has been conclusively proven effective.
For most patients, treatment begins with general supportive measures such as adequate bed rest, maintaining hydration, and controlling fever or pain. Oral rehydration is recommended to prevent dehydration, though intravenous fluids may be required in patients with vomiting, altered consciousness, or poor oral intake. Analgesics and antipyretics like acetaminophen or ibuprofen are commonly used to manage fever, headache, and muscle aches. However, aspirin and other salicylates should be avoided, especially in children, due to the risk of Reye’s syndrome. Maintaining electrolyte balance and ensuring proper nutrition are also important to support immune recovery.
Continuous monitoring of vital signs such as temperature, blood pressure, heart rate, and respiratory rate is essential during the acute phase of illness. In patients with suspected meningitis or encephalitis, regular neurological assessments are critical for detecting early signs of deterioration, including changes in consciousness, seizures, or focal neurological deficits. Hospitalization is recommended for individuals exhibiting severe headache, neck stiffness, photophobia, or altered mental status to ensure close observation and rapid management of complications.
In severe or neurologically complicated cases, intensive supportive management may be required. Patients with signs of increased intracranial pressure (ICP) should have their head elevated to 30 degrees, and osmotic agents such as mannitol can be administered to reduce cerebral edema under careful supervision. Oxygen therapy may be indicated for those with respiratory distress or hypoxia. Seizures, if present, should be managed using anticonvulsants such as benzodiazepines or phenytoin, following standard neurological protocols. In rare cases of persistent or refractory seizures, admission to an intensive care unit (ICU) for continuous monitoring may be necessary.
Currently, no antiviral medication has been approved specifically for LCMV. The antiviral drug ribavirin has demonstrated some in vitro activity against arenaviruses, including LCMV, but clinical evidence supporting its use remains inconclusive. Limited case reports suggest potential benefit in severe or immunocompromised patients; however, its application is not routinely recommended due to uncertain efficacy and possible toxicity. If used, it must be administered under strict medical supervision, typically in a research or compassionate-use context.
Management becomes more complex in immunocompromised individuals, particularly organ transplant recipients. In these cases, the infection can progress rapidly and may be fatal. Treatment strategies involve reducing immunosuppressive therapy to partially restore immune function while balancing the risk of graft rejection. Supportive measures such as ventilatory support, hemodynamic stabilization, and correction of metabolic imbalances are vital.
In pregnant women, LCMV poses a serious risk due to vertical transmission from mother to fetus, which can result in congenital infection characterized by hydrocephalus, chorioretinitis, intracranial calcifications, and severe neurodevelopmental defects. Unfortunately, no antiviral treatment has been proven effective in preventing or treating congenital infection.
Prognosis
The prognosis for lymphocytic choriomeningitis varies widely. Immunocompetent patients often recover fully with supportive care, experiencing mild to moderate symptoms that resolve in 1 to 2 weeks. Long-term neurological complications are rare in this group.
In contrast, immunocompromised individuals or those with severe CNS involvement face increased risks, including persistent neurological deficits or death. Early detection and management improve outcomes. The risk of fetal infection in pregnant women can result in miscarriage or congenital defects, requiring careful monitoring.
Historical Background
Lymphocytic choriomeningitis virus (LCMV), and the disease it causes (lymphocytic choriomeningitis, “LCM”), have a storied history in virology and immunology. The first isolation of the virus dates back to 1933, when Charles Armstrong, while investigating an outbreak of encephalitis in St. Louis, Missouri, serendipitously isolated a novel “filterable agent” from brain tissue. That agent was later identified as the cause of aseptic meningitis rather than the epidemic’s primary etiological virus.
In 1934, Armstrong coined the term lymphocytic choriomeningitis, reflecting the lymphocytic infiltration of the meninges and choroid plexus observed histologically in infected brains.
Shortly thereafter, Rivers and Scott confirmed the link between this virus and human cases of aseptic (nonbacterial) meningitis.
By the mid-1930s, Traub and others had shown that many mouse colonies harbored a similar or identical agent, thus linking rodent reservoirs to what was initially a puzzling human neurologic syndrome.
Over the ensuing decades, the virus came to play a central role in immunology research: it became the “model” virus for studying persistent infection, T cell exhaustion, viral persistence, major histocompatibility complex (MHC) restriction, and immunopathology.
In the 1950s and 1960s, more human cases, especially among laboratory workers exposed to rodents or rodent tissues were documented, reinforcing the zoonotic risk.
The advent of more sensitive virologic and serologic methods in the later 20th century broadened detection of LCMV and improved epidemiologic understanding, though the virus remains under-recognized in many settings
LCMV has a global distribution wherever its rodent hosts exist. It is most commonly reported in temperate regions of Europe, North America, and parts of Asia. Infection rates vary depending on rodent population density and human exposure.
Outbreaks tend to occur regionally and seasonally, often linked to increased contact with rodents in homes, laboratories, or pet stores.
Complications and Risk Factors
Lymphocytic choriomeningitis virus (LCMV) infection can lead to serious health issues, especially affecting the nervous system, vulnerable patients, and unborn children. These complications vary based on individual immune status and timing of infection.
Neurological Complications
The most distinctive feature of symptomatic LCMV disease is its neurotropism—its tendency to affect the central nervous system (CNS). In postnatal infections, a biphasic pattern is commonly observed. The illness often begins with a mild, flu-like prodrome characterized by fever, malaise, myalgia, and lack of appetite. After a short remission, a second phase may develop, marked by the sudden onset of neurological symptoms such as headache, stiff neck, photophobia, nausea, and vomiting. In more severe cases, altered consciousness, seizures, and confusion may occur, indicating encephalitic involvement.
Aseptic meningitis and meningoencephalitis are the primary neurological manifestations of LCMV. These conditions result from the immune system’s inflammatory response to the virus rather than direct cytopathic effects. While many patients eventually recover, some experience prolonged convalescence and residual neurological deficits. Rare complications such as transverse myelitis, ascending paralysis, and bulbar paralysis have also been reported, particularly in severe or untreated cases.
In congenital infections, neurological complications are far more devastating. When infection occurs during fetal development, the immature immune system and developing brain make the fetus highly susceptible to extensive neuronal damage. Post-infectious sequelae, including motor dysfunction, developmental delay, and cognitive impairment, are common in survivors.
Hydrocephalus and ventriculomegaly are frequently observed in congenital cases. These conditions result from impaired cerebrospinal fluid flow due to inflammation and scarring within the ventricles. Surgical intervention is often necessary to relieve intracranial pressure. Developmental delays, both cognitive and motor may persist throughout life. Although less common, postnatal infections can also result in long-term deficits, especially when the brain inflammation is severe.
While the CNS is the primary target, LCMV is capable of affecting other organs. Hepatic involvement, manifesting as elevated liver enzymes or hepatitis, has been observed in some patients, particularly those with compromised immune systems. This highlights the virus’s potential for systemic spread in specific host conditions.
Immunocompromised Patients
Individuals with weakened immune systems are at heightened risk for severe and disseminated LCMV infection. This group includes organ transplant recipients, individuals undergoing immunosuppressive therapy, and patients with diseases such as HIV/AIDS. In such cases, the virus may evade immune clearance and replicate unchecked, resulting in widespread organ damage and high mortality rates.
Transplant-associated LCMV infections have drawn particular attention in recent decades. Several outbreaks have occurred in which organs from an infected donor transmitted the virus to multiple recipients. These recipients often developed encephalitis, seizures, multi-organ failure, and, in many instances, fatal outcomes. Because LCMV is not routinely screened for in organ donors, undetected infections can have catastrophic consequences.
In immunosuppressed individuals, LCMV may persist for prolonged periods, leading to chronic infection and sustained viral shedding. The virus can disseminate beyond the CNS to involve organs such as the liver, lungs, and kidneys. The resulting clinical picture may include severe hepatitis, pneumonitis, or systemic inflammatory responses. Mortality rates in these populations are significantly higher compared to immunocompetent patients.
Given these risks, heightened clinical suspicion and early diagnostic evaluation are crucial in transplant medicine and immunocompromised care. Preventive measures such as thorough donor screening, improved rodent control, and rapid investigation of unexplained febrile illnesses in recipients are key to preventing future cases.
Risks in Pregnancy and Congenital Infection
One of the most serious concerns associated with LCMV is its potential to cause congenital infection. When a pregnant woman contracts LCMV, especially during the first or second trimester, the virus can cross the placental barrier and infect the developing fetus. The outcome depends on the timing of infection: early gestational exposure often leads to miscarriage or stillbirth, while later infection can cause severe developmental anomalies known as congenital LCMV syndrome.
Congenital LCMV typically manifests with a triad of neurological and ocular abnormalities. The most common findings include hydrocephalus or ventriculomegaly, intracranial calcifications (particularly in the periventricular region), and chorioretinitis, an inflammation of the retina that can result in permanent visual impairment. Other features may include microcephaly, cortical malformations, brain atrophy, and seizures. Survivors often suffer from long-term neurological deficits, such as intellectual disability, motor dysfunction, and sensory impairments including hearing loss.
Many infants affected by congenital LCMV are initially misdiagnosed with other congenital infections such as toxoplasmosis, cytomegalovirus (CMV), or Zika virus, because the clinical and radiologic features overlap significantly. As a result, congenital LCMV remains underrecognized, with the true burden likely higher than reported.
Epidemiology and Outbreaks
Serologic surveys indicate that human exposure to LCMV is more common than clinical recognition suggests. In the United States, antibodies against LCMV have been found in approximately 2–5 % of the general population, reflecting prior asymptomatic or mild infections. Broader global studies show that prevalence varies considerably by geography and population group.
In certain European regions, particularly in parts of Eastern and Southern Europe, seroprevalence has ranged from 0.2 % to 36 %, with the higher rates observed in areas where rodent infestation is common. For example, a study from an Adriatic island in Croatia reported an exposure rate near 36 %, while blood donor studies in France and New York showed much lower rates—0.2–0.33 %. These disparities highlight the influence of environment, housing conditions, and occupational exposure.
In the United States, approximately 5–10 % of house mice carry the virus. In pet and laboratory rodent colonies, infection rates of 2–3 % have been recorded during outbreak investigations.
Rodent infection is typically lifelong when acquired congenitally or early after birth. Such animals excrete the virus continuously in their urine, feces, saliva, and nasal secretions, contaminating surfaces, nesting materials, and food supplies. Humans primarily acquire infection through inhalation of aerosolized viral particles from dried rodent excreta or through direct contact with contaminated materials. Bites and organ transplantation from infected donors have also been documented as transmission routes.
Outbreaks are generally localized and focal, reflecting limited human-to-human transmission potential. A notable outbreak occurred in the United States between 1973 and 1974, when 181 human cases were identified across 12 states. The infections were traced to pet hamsters infected by wild mice in a single breeding facility, underscoring how commercial rodent operations can amplify transmission.
Another well-documented episode took place in 1989 at a U.S. cancer research center, where 7 of 82 laboratory staff tested positive for LCMV exposure after working with infected research mice; two required hospitalization.