PEDIATRICS Vol. 105 No. 3 March 2000, p. e35
ELECTRONIC ARTICLE:
Lymphocytic Choriomeningitis Virus: Reemerging Central Nervous
System Pathogen
From the Department of Pediatrics, and Steele Memorial Children's Research Center, University of Arizona, Tucson, Arizona.
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ABSTRACT |
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Lymphocytic choriomeningitis virus (LCMV), a human zoonosis caused by a rodent-borne arenavirus, has been associated with both postnatal and intrauterine human disease. Infection in man is acquired after inhalation, ingestion, or direct contact with virus found in the urine, feces, and saliva of infected mice, hamsters, and guinea pigs. Congenital LCMV infection is a significant, often unrecognized cause of chorioretinitis, hydrocephalus, microcephaly or macrocephaly, and mental retardation. Acquired LCMV infection, asymptomatic in approximately one third of individuals, is productive of central nervous system manifestations in one half of the remaining cases. Aseptic meningitis or meningoencephalitis are the predominant syndromes, although transverse myelitis, a Guillain-Barré-type syndrome, as well as transient and permanent acquired hydrocephalus have also been reported. Fatalities are rare. We report a patient with meningoencephalitis attributable to LCMV and discuss the spectrum of central nervous system disease, newer diagnostic modalities, and preventive strategies. lymphocytic choriomeningitis virus, aseptic meningitis, meningoencephalitis, zoonosis, hydrocephalus, arenavirus.
Lymphocytic choriomeningitis virus (LCMV), a rodent-borne
arenavirus, has recently been recognized as a human teratogenic pathogen.1-4 The devastating sequelae of congenital
infection include chorioretinitis, hydrocephalus, microcephaly or
macrocephaly, intracranial calcifications, mental retardation, and
seizures. Acquired LCMV disease, however, has received relatively scant
attention.1,5 We report a patient with meningoencephalitis
caused by LCMV to increase physician awareness of this potentially
preventable infection. This case also illustrates the diagnostic
conundrum LCMV infection may pose, when the initial history of illness
does not elicit rodent exposure.
A 17-year-old girl was referred for admission to University
Medical Center on December 26, 1998 with a 1-week history of headache, dizziness, nausea, vomiting, tactile fever, and cerebrospinal fluid
(CSF) pleocytosis noted on lumbar puncture. The patient had ingested
nonsteroidal antiinflammatory drugs with only temporary relief. She
denied concurrent upper respiratory symptoms, diarrhea, or rash. At the
referring institution a complete blood count, serum electrolytes, and
lumbar puncture were performed. Hemoglobin was 14.2 g/dL; hematocrit
was 40.2%; and white blood cell count was
16 500/mm3 with 84% polymorphonuclear cells,
9% lymphocytes, and 7% monocytes; platelet count was
364 000/mm3. CSF contained 1 red blood cell and
9760 white blood cells/mm3 (100% mononuclear
cells). CSF protein was 231 mg/dL; glucose was 58 mg/dL; and serum
glucose was 137 mg/dL. No organisms were seen on Gram stain. The
patient received 1 g of ceftriaxone before transport. On admission
to University Medical Center her temperature was 37.5°C, heart rate
80 beats per minute, respiratory rate 16 per minute, and blood pressure
108/68 mm Hg. She had normal fundoscopic and neurologic examinations
with the exception of mild hyperreflexia. Her neck was supple with full
range of motion.
Additional questioning of the patient revealed significant exposure to
cats, dogs, and mice at home. Viral cultures of nasopharyngeal, ororpharyngeal, and rectal swabs and CSF; Coccidioides
immitis, Epstein-Barr virus, LCMV, mycoplasma, and
Bartonella henselae serologies were obtained. Intradermal
tuberculin skin test was placed. After 48 hours of hospitalization, the
patient's symptoms had resolved; CSF culture and tuberculin test
results were negative. She was discharged from the hospital with a
presumptive diagnosis of viral meningitis.
The patient was seen again ~3 weeks after discharge. She had no
headache but had persistent emesis, decreased food intake and a 2-lb
weight loss. Additional historical data included significant preillness
exposure to mouse droppings, via inhalation, and/or direct contact,
during a high school kitchen cleanup. Physical examination was
remarkable only for persistent hyperreflexia and moderate nystagmus on
lateral gaze. At that time, all laboratory test results, including
bacterial, mycobacterial, fungal cultures, and all serologies obtained
during hospitalization, were negative. However, LCMV antibody had been
determined by complement fixation. Therefore, the LCMV serology was
repeated by immunoflourescent antibody (IFA) technique. Repeat
mycoplasma serologies and a magnetic resonance imaging study of the
head were also performed and were negative. LCMV IFA was positive with
immunoglobulin M (IgM) >1:20 and an immunoglobulin G (IgG) LCMV disease is a zoonosis acquired by contact with infected mice,
hamsters, guinea pigs, and their excreta. Postnatal human infection is
asymptomatic in approximately one third of patients.6 Approximately one half of the remaining cases develop aseptic meningitis or meningoencephalitis, although transverse myelitis and the
Guillain-Barré syndrome have also been reported.7 Fatalities have been rare, as have been long-term sequelae, which have
included transient and permanent acquired hydrocephalus and deafness.1,8 Neuropathologic studies of human and animal
LCMV infection have demonstrated mononuclear cell infiltrates in
meninges, choroid plexus, and ependyma.1,9,10 These
observations may explain the obstructive hydrocephalus observed in both
congenital and acquired LCMV infections with central nervous system
involvement.
We suggest that LCMV infection of the central nervous system is
underdiagnosed. Between 1941 and 1958 in a study of hospitalized patients with aseptic meningitis, nearly 10% were attributable to
LCMV, and it was the most common cause during the winter months, presumably attributable to movement of mice indoors.11 There are no pathognomonic signs, symptoms, or laboratory abnormalities in this infection. Fever, headache, nausea, vomiting, and occasional photophobia are prominent symptoms. As in our patient, significant CSF
pleocytocytosis may occur, which is unusual in other viral infections.
CSF white blood cell counts have ranged from <30 to >3000, generally
predominantly mononuclear cells.12 Normal to slightly
decreased CSF glucose and slightly to moderately increased protein
concentrations have been noted. CSF eosinophilia has been reported in 1 infected child.13
This case also illustrates the importance of using appropriate and
sensitive diagnostic serologic tests. The complement fixation test for
LCMV, although widely available, is insensitive14,15 and
proved negative in our patient. Because of the strong suspicion of LCMV
infection, repeat testing using the more sensitive IFA test was
performed and revealed late acute or early convalescent LCMV infection
with both measurable IgM and IgG antibody in the first serum specimen
and only IgG antibody in the second (convalescent) specimen. A
sensitive, enzyme-linked immunosorbent assay, which measures LCMV IgM
and IgG is also available and performed at the Centers for Disease
Control and Prevention.2
LCMV infections may be prevented by public education of the need to
avoid contact with potentially infected rodents and their excreta.
After diagnosis of LCMV meningoencephalitis in our patient, Health
Department and school personnel were notified. Mousetraps were placed
in and around the high school and resulted in rapid abatement of the
rodent infestation problem.
Dr Black-Davis referred this patient; Craig E. Levy (Arizona
Health Department) trapped the mice; and Dr Besselsen performed the
antibody determinations in the mice. Amy O'Brien provided assistance
in manuscript preparation.
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CASE REPORT
1:256.
One month later, repeat LCMV IgM was <1:20 and IgG was unchanged at
1:256. Of note, 2 of 5 mice subsequently trapped at the high school
were LCMV antibody positive.
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DISCUSSION
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Abstract
Discussion
References
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ACKNOWLEDGMENTS
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FOOTNOTES |
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Received for publication Aug 9, 1999; accepted Sep 29, 1999.
Reprint requests to (L.L.B.) 1501 N Campbell Ave, POB 245073, Tucson, AZ 85724-5073. E-mail: llb{at}peds.arizona.edu
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ABBREVIATIONS |
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LCMV, lymphocytic choriomeningitis virus; CSF, cerebrospinal fluid; IFA, immunoflourescent antibody; IgM, immunoglobulin M; IgG, immunoglobulin G.
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REFERENCES |
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Pediatrics (ISSN 0031 4005). Copyright ©2000 by the American Academy of Pediatrics
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