Pediatric Lymphocytic Choriomeningitis Virus 

Updated: Aug 15, 2018
Author: J Michael Klatte, MD; Chief Editor: Russell W Steele, MD 

Overview

Background

Lymphocytic choriomeningitis virus (LCMV) is a single-stranded RNA virus of the family Arenaviridae. Other members of Arenaviridae include Lassa, Argentine hemorrhagic fever, Bolivian hemorrhagic fever, and Venezuelan hemorrhagic fever viruses. LCMV causes an asymptomatic infection in its rodent reservoir (eg, mice) and has variable effect on hamster health. It is passed to humans when they inhale, consume, or otherwise contact infected excreta. Typically a febrile, self-limited, biphasic disease, LCMV is a significant teratogen, whose role in congenital infections has only recently gained appreciation.[1] Individuals who are exposed to rodents from living conditions or other exposure, such as pet handlers and laboratory personnel, are at particular risk for infection. Transmission of infection during organ transplantation has been documented.[2, 3, 4]

Pathophysiology

After transmission of LCMV via inhalation, consumption, cutaneous or mucosal exposure, or organ transplantation, a primary viremia ensues, resulting in extra–CNS seeding and an initial, nonspecific, febrile illness. Several days later, secondary viremia follows and frequently results in CNS involvement and typical meningitis/meningoencephalitis.

The manifestations of the disease are thought to result from the host response to the virus as natural killer cells and cytotoxic T cells respond to infection with the production of interferon and additional inflammatory mediators.[5] No human-to-human transmission occurs, except in congenital disease or organ transplantation. Congenital LCMV infection is typically much more serious than the acquired disease. It can mimic toxoplasmosis and cytomegalovirus (CMV) congenital infection. As in acquired infection, congenital disease is thought to result from T-cell and B-cell–mediated injury to the fetal host. LCMV transmitted in utero likely demonstrates selective neurotropism, targeting the developing fetal brain and retina.[6]

Epidemiology

Frequency

United States

Seroprevalence was found to be 5% among adults at a sexually transmitted disease clinic in Baltimore, Maryland;[7] 5.4% among those older than 30 years in Birmingham, Alabama;[8] and 0.3% among those younger than 30 years in Birmingham, Alabama.[8] Seroprevalence in upstate New York was 0.4%.[9] Disease is more common in the fall and winter months (when rodents seek shelter indoors), and depends on rodent populations. Prevalence of intrauterine infections is unknown.

International

Disease has been reported in North and South America and Europe. Seroprevalence was 4% in Nova Scotia,[10] 1-3.6% in Argentina,[11] and 1.7% in Spain.[12]

Mortality/Morbidity

Less than 1% of patients with acquired infection have fatal disease, usually encephalitis or massive hemorrhage. By contrast, 35% of congenital infections are believed to result in fetal loss, and mortality in transplant-acquired infection is substantial. Most surviving infants (84%) have neurodevelopmental sequelae, including cerebral palsy, seizures, decreased visual acuity, mental retardation, and progressive hydrocephalus.[13]

Race

LCMV has no racial predilection.

Sex

LCMV has no gender predilection.

Age

Disease is most common among young adults, although infection may occur in individuals of any age.

 

Presentation

History

Acquired lymphocytic choriomeningitis virus (LCMV) infection

One third of infections are subclinical.

One half of the clinical infections have neurologic involvement.

The typical biphasic disease is composed of a nonspecific influenza-like illness, followed by typical viral aseptic meningitis.

The first phase includes a fever, a headache, lymphadenopathy, and a maculopapular rash lasting 3-5 days.

A more severe headache, photophobia, a stiff neck, vomiting, and lethargy follow after approximately 4 days.

Patients may have a history of rodent exposure 1-3 weeks earlier (often 6-13 d, but may extend to 3 wk).

Other symptoms commonly seen include more prolonged fevers, malaise, myalgias, nausea or vomiting, a retro-orbital headache, anorexia, weakness, a sore throat, a cough, and seizures.

Unusual symptoms include orchitis, parotitis, pancreatitis, myocarditis, paresis or paralysis, alopecia, and arthritis (involving the metacarpophalangeal and proximal interphalangeal joints).

Congenital infection

Approximately 50-63% of mothers remember having had a nonspecific influenza-like illness during pregnancy.

Approximately 25-46% of mothers remember having had rodent exposure.

Physical

Acquired infection

Typical findings are nonspecific.

A fever up to 102-104°F (39-40°C) is typical.

Relative bradycardia may be present.

Diffuse lymphadenopathy, a maculopapular rash, or both may be present.

Pharyngitis without exudates may occur.

A stiff neck is common with CNS involvement.

Unusual manifestations include arthritis of the metacarpophalangeal and proximal interphalangeal joints; hepatosplenomegaly; papilledema; deafness; paralysis; and findings suggestive of unilateral orchitis, viral myocarditis, pneumonitis, psychosis, transverse myelitis, Guillain-Barré syndrome, transient or permanent hydrocephalus, and encephalitis.

Congenital infection

Neonates are usually appropriate for gestational age and are born at term.

Approximately 88-93% of infants have chorioretinopathy and/or other ocular manifestations, including chorioretinitis, scarring, atrophy, nystagmus, esotropia, microphthalmos, cataracts, and vitreitis.[14]

Approximately 34-43% of infants have macrocephaly.[14]

Hydrocephalus or intracranial periventricular calcifications have been documented in approximately 90% of infants who have undergone imaging studies.

Approximately 13-38% of infants have microcephaly, which is usually due to cortical dysplasia or atrophy.[14]

Hearing loss occurs in approximately 7% of cases, is typically bilateral and sensorineural, and auditory deficits in those affected range from severe to profound.[15]

Lack of involvement of multiple organ systems (namely, rarity of skin rashes, hepatosplenomegaly, and/or cardiac involvement) helps to differentiate congenital LCMV from other congenital infections.[1]

Causes

Exposure to the virus in feces, urine, semen, saliva, rodent blood, or transplanted organs[16] may result in human infection. Those with occupational exposure to mice are at risk for infection.[17]

 

DDx

 

Workup

Laboratory Studies

The following studies are indicated in lymphocytic choriomeningitis virus (LCMV)

CBC count

Findings may include leukopenia, thrombocytopenia, or both early in infection.

Liver function tests

Findings may show mildly elevated serum transaminase and bilirubin levels.

Serology tests

An immunofluorescence assay that detects both immunoglobulin G (IgG) and immunoglobulin M (IgM) is commercially available and is the preferred test.

An enzyme-linked immunosorbent assay for IgM and IgG on serum or cerebrospinal fluid (CSF) is available at the Centers for Disease Control and Prevention.

A complement fixation assay exists but is insensitive and its use is discouraged for congenital and acquired infection.

The virus may be isolated from blood early in infection, from CSF later in infection, and, rarely, from urine or nasopharyngeal specimens using cell culture or direct intracerebral inoculation of weanling mice.

CSF examination

Elevated protein levels may be found.

Glucose levels are low in 25% of patients and are within the reference range in 75% of patients.

Lymphocytic pleocytosis is typical, with less than 30 to more than 8000 WBCs present.

One case of eosinophilic meningitis has been reported.

Polymerase chain reaction

This modality is used in research laboratories for the detection of the virus. A clinical assay is being validated.[18]

Imaging Studies

Brain CT scanning

CT findings in infants with congenital LCMV infection may include noncommunicating hydrocephalus, cortical dysplasia and microcephaly, periventricular calcifications, and/or cerebellar hypoplasia.

Hydrocephalus or intracranial calcifications occur in 89% of affected newborns.[14]

Chest radiography

Diffuse infiltrates are rarely depicted.

Procedures

Lumbar puncture

Findings may reveal increased opening pressure and provide CSF for testing.

Biopsy

For solid organ transplant recipients with suspected LCMV infection:

Biopsy of the transplanted organ, followed by immunohistochemical staining of the biopsy specimen, may reveal LCMV antigens within the affected donor organ tissues.[2]

Histologic Findings

The leptomeninges are infiltrated by lymphocytes and histiocytes with few polymorphonuclear cells. This mononuclear cell infiltration may involve the meninges, choroid plexus, and ependyma.

Brain involvement results in infiltration of the perivascular Virchow-Robin spaces, cerebromalacia, neuroanalysis, glial proliferation, and perivascular edema.

Distinct findings in the fetus may include lymphocytic myocarditis and extramedullary hematopoiesis.

 

Treatment

Medical Care

Care is primarily supportive and symptomatic.

Consultations

Consultations with an infectious diseases specialist, ophthalmologist, and neurologist are recommended.

 

Medication

Medication Summary

No specific treatment for lymphocytic choriomeningitis virus (LCMV) infection is available. Early data suggest that the virus is susceptible to ribavirin in vitro, but little information on the treatment of infected humans is available. Despite this, and despite the fact that no large-scale determination has been made regarding the efficacy of ribavirin use in transplant-acquired LCMV, the recommended treatment for these patients includes reduced immunosuppression and ribavirin.[3, 19]

In vitro studies on favipiravir (a compound shown to inhibit LCMV replication) and experimental pyrimidine biosynthesis inhibitors show promising potential for these agents as future LCMV treatment options in humans.[1, 20]

 

Follow-up

Transfer

Transfer to another facility should be considered for patients with lymphocytic choriomeningitis virus (LCMV) infection if the required personnel are not locally available.

Deterrence/Prevention

Rodent control measures significantly decrease disease incidence.

Preventing exposure to rodent excreta decreases disease incidence.

Laboratory personnel who handle rodents should be aware of the disease and use appropriate barrier precautions.

Standard precautions are appropriate for hospitalized patients.

Early vaccine development efforts are underway.[21]

Complications

Congenital infection is a significant complication of the disease in pregnant women. For example, LCMV is likely an underrecognized cause of nonimmune hydrops.[6]

CNS manifestations of the disease may include encephalitis, Guillain-Barré syndrome, transverse myelitis, paralysis, seizures, and hydrocephalus.[22]

Rare complications of acquired infection include deafness, parotitis, myocarditis, and pneumonitis.

Prognosis

Prognosis is excellent for recovery in almost all cases (except congenital or transplant-associated cases). However, patients may have a period of fatigue, dizziness, and headache that lasts weeks to months following acute disease.[23]

Patient Education

Pregnant women should be warned about contact with rodents and rodent excreta.

Laboratory personnel should use barrier precautions when they handle rodents or are exposed to rodent excreta.