Lymphocytic Choriomeningitis Virus (LCMV) Infection 

Updated: Sep 11, 2017
Author: Philip J McDonald, MD; Chief Editor: Burke A Cunha, MD 

Overview

Background

Lymphocytic choriomeningitis virus (LCMV) was first isolated in 1933 from a patient suspected to have St. Louis Encephalitis.[1] It is a single-stranded RNA virus that belongs to the family Arenaviridae (so named because of their appearance on electron microscopy, which, owing to host ribosomes, resemble grains of sand).[2]

Other members of the Arenaviridae family include the Lassa virus (LASV) and the New World complex viruses (Junin, Machupo, Guanarito, Sabia). Infection with LCMV results in a febrile, self-limited, biphasic disease that is often complicated by aseptic meningitis. Infected but asymptomatic (carrier state) rodents, most commonly mice (Mus domesticus, Mus musculus), hamsters, and Guinea pigs, serve as reservoirs for LCMV.[3, 4]

LCMV is most commonly transmitted via inhalation of infected excreta. Direct contact and animal bites are a potential route of LCMV infection in pet handlers and laboratory technicians.[4, 5]

Pathophysiology

The initial viremia of LCMV infection (phase 1) extensively seeds extra-CNS tissue. The secondary viremia (phase 2) infects the meninges and, less commonly, the cortical tissue. The leptomeninges are infiltrated mainly by lymphocytes and histiocytes, with few neutrophils. In LCMV encephalitis, the same type of inflammatory cells is observed in the perivascular Virchow-Robin spaces. LCMV is not cytotoxic. It appears that the host's immune response to the infected cells produces the various manifestations of this disease. Natural killer (NK) cells are first to respond, followed by the production of interferon by cytotoxic T cells. LCMV antibodies become detectable during the second febrile episode. In addition, LCMV can suppress the production of acetylcholine neuronal cells in cell culture.[6, 7, 8, 9, 10]

LCMV may affect the autonomic nervous system, various sensory modalities, and cranial nerves. Rarely, the virus can cause long-term neurologic sequelae, including chronic headache, hydrocephalus, deafness, transverse myelitis, and Guillain-Barré syndrome.[11] Other organs, especially the testes, heart, and joints, may be involved. Orchitis is usually unilateral and develops 1-3 weeks after illness onset. Cardiac involvement can occur in the form of viral myocarditis or pericarditis. The metacarpophalangeal joint and the proximal interphalangeal joint are the most common sites of arthritis caused by LCMV. The objective swelling, redness, and pain resolve within a few weeks.[8, 9, 12]

Vertical transmission of LCMV during pregnancy has been associated with increased risk of spontaneous abortion. It can also cause a syndrome of hydrocephalus, chorioretinitis, and perivascular calcifications similar to that seen in congenital cytomegalovirus (CMV) infection and toxoplasmosis, potentially leading to mental retardation, microcephaly, seizures, and blindness.[13]

In solid organ transplant recipients with donor-derived infection (DDI), LCMV has been shown to cause severe illness characterized by multisystem organ failure.[14] Meningitis is a less-prominent feature in these individuals. Their high degree of morbidity and mortality can be attributed to profoundly decreased cell-mediated immunity due to immunosuppression.

Epidemiology

Frequency

United States

The exact incidence of LCMV infection is unknown, although the seroprevalence is approximately 5%. Local variations in seropositivity for LCMV (2%-5%) depend on the local rodent populations.[15] The true prevalence of LCMV infection is suspected to be higher because of underreporting and missed diagnoses; 10% or more cases of aseptic meningitis may be due to LCMV.[16] LCMV infection in humans is most common in autumn owing to migration of mice into warm structures.[9]

International

LCMV infections have been reported in North America, South America, Europe, Australia, and Japan.[9, 17, 18]

Mortality/Morbidity

LCMV infection carries a mortality rate of less than 1%. Death may be attributable to complications of encephalitis or to a hemorrhagic syndrome. As with other arenaviruses, immunosuppression may predispose to a syndrome of multisystem organ failure including hemorrhage.[16]

Race

LCMV infection has no racial predilection.

Sex

LCMV infection has no sexual predilection.

Age

LCMV infection is more common in young adults, although illness may occur in any age group.[9]

 

Presentation

History

Clinical manifestations of lymphocytic choriomeningitis virus (LCMV) infection in immunocompetent individuals range from a flulike illness to severe CNS involvement with meningoencephalitis. Phase 1 of LCM typically manifests as fever and headache, often with lymphadenopathy and a maculopapular rash, resolving after 3-5 days. In many patients, a more severe headache returns within 2-4 days, associated with typical signs of aseptic meningitis.[6, 8, 9, 16]

Patients with LCMV infection may report a history of exposure to rodents, hamsters, or the excreta of these animals 1-3 weeks before the onset of symptoms. Infection is most common in the autumn. Smoking is a risk factor.[19] Approximately one third of LCMV infections cause no symptoms, and up to one half of infected individuals have a nonspecific febrile illness without neurologic involvement. The remainder of patients experience classic biphasic symptoms associated with LCMV infection and meningitis or encephalitis.

Initial nonspecific symptoms of LCMV infection include the following:

  • Fever
  • Malaise
  • Myalgias
  • Nausea or vomiting
  • Retro-orbital headache
  • Photophobia
  • Anorexia

Symptoms may subside for 2-4 days and then recur with the following:

  • Increased headache
  • Nuchal rigidity
  • Decreased level of consciousness ranging from lethargy to coma
  • Occasionally, patients develop the following:
    • Orchitis
    • Parotitis
    • Myocarditis or pericarditis
    • Paresis or paralysis (extremely rare)
    • Alopecia
    • Arthritis of the hand

Immunosuppressed individuals (eg, solid organ transplant recipients) may develop a syndrome of multisystem organ involvement including the following:[20, 16]

  • Encephalitis/seizures
  • Respiratory failure
  • Leukopenia
  • Thrombocytopenia
  • Coagulopathy
  • Renal/liver dysfunction
  • Hemorrhagic foci in multiple tissues

Neurologic sequelae are rare but may include chronic headache, hydrocephalus, deafness, transverse myelitis, and Guillain-Barré syndrome.[11]

Complete recovery within 1-3 weeks is the rule, although convalescence may be prolonged.

Physical

Typical clinical features of LCMV infection are as follows:[6, 8, 9]

  • Fever (generally 39-40°C)
  • Relative bradycardia
  • Nonexudative pharyngitis
  • Papilledema (rare)
  • Nuchal rigidity (mild)
  • Erythematous maculopapular rash (rare)
  • Lymphadenopathy

Atypical clinical features of LCMV infection include the following:

  • Alterations in function of cranial, sensory, or autonomic nerves
  • Encephalitis manifesting as paraplegia or psychosis

Causes

Infection is caused by the lymphocytic choriomeningitis virus (LCMV), a member of the family Arenaviridae.

Transmission is generally via inhalation of LCMV virions in the aerosolized excreta (urine or feces) from chronically infected rodents.[9]

Transmission is also possible through close contact with infected animals, via direct inoculation through the skin or mucous membranes.

Populations at high risk of LCMV infection include the following:

  • Individuals in locations with large mouse populations, particularly those who directly maintain homes and other properties.
  • Laboratory workers involved in the handling of mice or hamsters
  • Workers at facilities that breed mice for research or feeding purposes [19]
  • Six clusters (five in the United States) of donor-derived infection in solid organ transplant recipients [20, 14]
 

DDx

Diagnostic Considerations

Table 1. Differential Diagnosis of Lymphocytic Choriomeningitis (Open Table in a new window)

Diagnosis

Season

Usual Source

Relative Bradycardia

Pharyngitis

Diarrhea

Parotitis

Orchitis

CSF Glucose level

LCMV infection

Fall/winter

Mouse, hamster

+

+/-

-

+/-

+/-

Normal or decreased

Typhoid fever

Year-round

Food, water

+

+

+ (late)

-

-

Normal

Enteroviral illness

Summer

Water

-

+

+

-

-

Normal

Arboviral illness†

Summer

Mosquito

-

-

-

-

-

Normal

Leptospirosis

Summer/fall

Dogs, rats

-

-

-

-

-

Normal

Influenza

Winter

Person

-

+

-

-

-

Normal

Mumps

Winter/spring

Person

-

-

-

+

+/-

Normal or decreased

†Including West Nile virus (WNV), Japanese encephalitis virus (JEV), St. Louis encephalitis virus (SLEV), Zika virus (ZIKV), Yellow fever virus (YFV), Western and Eastern equine encephalitis (WEE, EEE)

Other causes of aseptic meningitis (eg, herpes simplex virus (HSV), varicella-zoster virus (VZV), syphilis, Cryptococcus, Coccidioides immitis, Mycobacteria tuberculosis, malignancy, NSAIDs/other medications) should also be considered based on the history.

Differential Diagnoses

 

Workup

Laboratory Studies

Lymphocytic choriomeningitis virus (LCMV) infection is initially diagnosed based on a suggestive history that is confirmed by various laboratory investigations.[9]

Complete blood cell (CBC) count may reveal leukopenia and thrombocytopenia early in the course of illness.

The preferred diagnostic modality is assessment of acute and convalescent immunoglobulin M (IgM) and immunoglobulin G (IgG) titers from both the serum and cerebrospinal fluid (CSF). The sensitivity of enzyme-linked immunosorbent assay (ELISA) is greater than that of immunofluorescence (IFA)–based assays. Complement fixation is insensitive and should not be used.[15]

Immunohistochemical staining, virus culture, and reverse transcription-polymerase chain reaction (RT-PCR) of tissues may be useful.

Typical findings of lumbar puncture are as follows:[9]

  • Elevated opening pressure, occasionally with papilledema
  • Protein concentration from 50-300 mg/dL (can exceed 600 mg/dL) [11]
  • Lymphocytic pleocytosis with several hundred cells/µL (range, 10 to >3000 cells/µL)
  • Hypoglycorrhachia (in fewer than one third of patients)
 

Treatment

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]

 

Follow-up

Further Inpatient Care

Patients with severe meningoencephalitis are usually hospitalized.

Deterrence/Prevention

Rodent control measures decrease the frequency of lymphocytic choriomeningitis virus (LCMV) infection.[9]

Laboratory personnel who handle mice or hamsters are at increased risk for LCMV infection. No established method of preventing infection in these situations exists. Prudence dictates the use of gloves when handling these animals, especially if the person's hands are abraded. If the risk of infection is high, consider the use of a personal respirator.

No method is effective to prevent transmission by organ transplantation since determination of pet rodent ownership by the donor is neither sensitive or specific. Testing tissue with RT-PCR and immunohistochemical analysis is extremely expensive and may not necessarily be effective.

Prognosis

Lymphocytic choriomeningitis (LCM) is rarely fatal; the overall prognosis is excellent.

Patients with encephalitis are at higher risk for neurologic sequelae.

Convalescence may be prolonged, with continuing dizziness, somnolence, and fatigue.

Severe disease leading to death has been reported in immunocompromised patients and organ transplant recipients (7 of 8 infected patients died).[23]

Patient Education

Avoid exposure to rodent secreta and excreta.