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Internal Page links:
Lymphocytic Choriomeningitis Virus: An Unrecognized Teratogenic Pathogen
    Infection distribution in urban Baltimore 1992
LCM Detected Serologically in Iowa Infant
    Symptoms
Lymphocytic Choriomeningitis Virus
Lymphocytic Choriomeningitis from Netvet
LYMPHOCYTIC CHORIOMENINGITIS VIRUS & BIRTH DEFECTS - USA
Taxonomy
Lymphocytic Choriomeningitis from CaringTogether
In Guinea Pigs
Rodent Testing
Other References
Some word definitions:

EID Volume 1 * Number 4                              October-December 1995
Dispatches

Lymphocytic choriomeningitis virus (LCMV), the first member of the arenavirus family to be isolated, is the causative agent of a zoonosis acquired from chronically viremic mice or hamsters (1).
The clinical spectrum of acquired human LCMV infection ranges from inapparent and asymptomatic to, in rare instances, severely symptomatic, systemic, and fatal central nervous system (CNS) disease. Intrauterine LCMV infection has resulted in fetal or neonatal death, as well as hydrocephalus and chorioretinitis in infants (2-6). We have diagnosed congenital LCMV infection in three infants (7) and have collated published and unpublished data on three additional affected infants (8, G.R. Istre, pers. comm.). This report briefly summarizes the salient features of the infection in five of these six American infants and outlines the similarities between these and features observed earlier in Europe. We suggest that LCMV is a more frequent cause of CNS disease in newborns than previously recognized.

Congenital LCMV infection was first recognized in Great Britain in an infant who died at  2 days of age (3). Subsequently, fetal infection with spontaneous abortion (2) and congenital infection in liveborn infants with hydrocephalus and chorioretinitis were documented in Germany (4), France (6), and Lithuania (5). We have recently documented congenital LCMV infection in three infants from Arizona (7) and have obtained information regarding three additional neonates from Arizona, Nebraska (8), and Texas (G.R. Istre, pers. comm.). Detailed clinical and laboratory data are available for five of the six infants. All displayed nonobstructive hydrocephalus with periventricular calcifications, chorioretinitis, and psychomotor retardation. One of the five infants had sensorineural deafness. None of the infants had cardiac abnormalities. Two infants have had follow-up ophthalmologic and audiologic examinations which have shown neither the progression of chorioretinitis nor the development of new auditory deficits. Toxoplasma gondii, cytomegalovirus, Herpes simplex virus, rubella, enterovirus, and Treponema pallidum infections were excluded by culture or serology in all infants. The diagnosis of congenital LCMV infection was confirmed in all infants by immunofluorescence antibody (IFA) and enzyme-linked immunosorbent assays (ELISAs).  In addition, serum, CSF, urine, and throat wash specimens from two infants were injected into Vero cell monolayers. Neither cytopathic effect nor LCMV antigens were detected after incubation.  Because virus isolation was only attempted after the disease was first diagnosed when the children were 10 months of age, failure to isolate LCMV was not unanticipated.
Laboratory diagnosis of LCMV infection is generally made by serologic techniques. IFA is a more sensitive diagnostic method than either complement fixation or neutralizing antibody techniques (9,10). The newer ELISAs are now being used to evaluate congenitally infected infants. Testing the child's serum and CSF and a simultaneously obtained serum specimen from the mother yields the maximum information if done as soon after birth as possible.

The mothers of four of the five infants in this report had a history of febrile illness during pregnancy, in contrast to a minority of mothers of affected infants previously reported. Typical LCMV infection in adults is a biphasic disease with fever, malaise, myalgias, anorexia, nausea, vomiting, pharyngitis, cough, and adenopathy followed by defervescence and a second phase of CNS disease. However, CNS symptoms may appear without any prodrome or may never develop.

Meningitis and meningoencephalitis are the most frequent neurologic manifestations of disease, although myelitis, Guillain-Barr -syndrome, and sensorineural deafness have been reported (11). Between 1941 and 1958, 8% to 11% of viral CNS syndromes in hospitalized patients in a Washington, D.C., medical center were etiologically associated with LCMV (12). Arthritis, parotitis, orchitis, myocarditis, and rash have also been noted (13). Clinical interest in LCMV, however, has not been maintained, and the disease is rarely considered despite improved serodiagnostic methods.

Although a history of contact with rodents and their excreta is of diagnostic utility, it is not universally present. A maternal history of rodent exposure was elicited for three of our five infants. Wild mice (Mus musculus) and hamsters infected in utero with LCMV during maternal viremia develop both persistent viremia and viruria. The virus is transmitted to humans by direct animal contact; by contact with infected rodent saliva, nasal secretions, urine, feces, semen, and milk; and by infectious aerosols (1). Human-to-human transmission has not been documented. The distribution of LCMV is highly variable within mouse populations. Seasonal, annual, and cyclical variations in rodent density and infection have been postulated but remain inadequately studied (14). LCMV spreads to humans in rural settings or when human habitats are substandard. Infected laboratory and pet rodents have also been associated with disease in humans(1). Serologic surveys and clinical studies have documented both epidemic and endemic human infection in Europe and the Americas. In Baltimore, 9.0% of house mice and 4.7% of residents have had measurable LCMV antibody (15,16).

We hypothesize that congenital LCMV infection is generally undiagnosed and may account for unexplained hydrocephalus with microcephaly or macrocephaly, deafness, blindness, and mental retardation (three of the five infants in this report were referred for infectious disease consultation by pediatric geneticists, and two were referred by pediatric neurologists). No accurate data are available regarding the prevalence and persistence of LCMV antibodies in unselected infants, children, and adults in diverse geographic locales or in children with unexplained visual and/or auditory deficits, microcephaly, and retardation. Increased recreational activities in rural environments, rehabilitation of and habitation in older rodent-infected domiciles, and acquisition of unscreened rodents for pets or laboratory use pose as yet undefined risks for LCMV infection to the fetus, child, and adult. The need for further research to define the frequency of LCMV infection in human and animal populations is clear. LCMV infection can best be prevented by educating the public and medical professionals on the hazards of contact with infected rodents.

                  Leslie L. Barton, M.D.,* C.J. Peters, M.D.,†
                         T.G. Ksiazek, D.V.M., Ph.D.†
                    *University of Arizona Health Sciences Center,
                     Department of Pediatrics and Steele Memorial
                   Childrens Research Center, Tucson, Arizona, USA;
                  †National Center for Infectious Diseases, Centers for
                 Disease Control and Prevention, Atlanta, Georgia, USA

Acknowledgments
We thank Drs. Jane Wilson, Gregory Istre, Stephen Chartrand, and Laurie Seaver for patients' information; Dr. Matafija Seinbergas for his enthusiastic support; and Ms. Amy Sites for technical support.

References
1. Jahrling PB, Peters CJ. Lymphocytic choriomeningitis: a neglected pathogen of man. Arch Pathol Lab Med 1992;116:486-8.
2. Ackermann R, Stammler A, Armbruster B. Isolierung von Virus der lymphozytaren
Choriomeningitis aus Abrasionsmaterial nach Kontakt der Schwangeren mit einem Syrischen Goldhamster (Mesocricetus auratus). Infection 1975;3:47-9.
3. Komrower GM, Williams BL, Stones PB. Lymphocytic choriomen- ingitis in the newborn:  probable transplacental infection. Lancet 1955;1:697-8.
4. Ackermann R, Korver G, Turss R, Wonne R, Hochgesand P. Prenatal infection with the lymphocytic choriomeningitis virus. Dtsch Med Wochenschr 1974;13:629-32.
5. Seinbergas MM. Hydrocephalus due to prenatal infection with the lymphocytic choriomeningitis virus. Infection 1976;4:185-91.
6. Chastel C, Bosshard S, Le Goff F, Quillien MC, Gilly R, Aymard M. Infection transplacentaire par le virus de la choriomeningite lymphocytaire: resultats dune enguete serologique retrospective en France. Nouv Press Med 1978;7:1089-92.
7. Barton LL, Budd SC, Morfitt WS, et al. Congenital lymphocytic choriomeningitis virus infection in twins. Pediatr Infect Dis J 1993;12:942-6.
8. Larsen PD, Chartrand SA, Tomashek KY, Hauser LG, Ksiazek TG. Hydrocephalus
complicating lymphocytic choriomeningitis virus infection. Pediatr Infect Dis J 1993;12:528-31.
9.Lewis VJ, Walter PD, Thacker WL, Winkler WG. Comparison of three tests for the serological diagnosis of lymphocytic choriomeningitis virus infection. J Clin Microbiol 1975;2:193-7.
10. Lehmann-Grube F, Kallay M, Ibscher B, Schwartz R. Serologic diagnosis of human infections with lymphocytic choriomeningitis virus: comparative evaluation of seven methods. J Med Virol 1979;4:125-36.
11. Lehmann-Grube F. Diseases of the nervous system caused by lymphocytic choriomeningitis virus and other arenaviruses. In: Handbook of clinical neurology. New York: Elsevier, 1989;12:355-81.
12. Meyer HM, Johnson RT, Crawford, IP, Dascomb HE, Rogers NG. Central nervous system syndromes of "viral" etiology: a study of 713 cases. Am J Med 1960:334-47.
13. Lewis JM, Utz JP. Orchitis, parotitis and meningoencephalitis due to lymphocytic-choriomeningitis virus. N Engl J Med 1961;265:776-80.
14.Childs JE, Peters CJ. Ecology and epidemiology of arenaviruses and their hosts. In: The Arenaviridae. New York: Plenum, 1993:331-84.
15. Childs JE, Glass GE, Korch GW, Ksiazek TG, Leduc JW. Lymphocytic choriomeningitis virus infection and house mouse (Mus musculus) distribution in urban Baltimore. Am J Trop Med Hyg 1992;47:27-34.
16. Childs JE, Glass GE, Ksiazek TG, Rossi CA, Barrera Oro JG, Leduc JW. Human-rodent contact and infection with lymphocytic choriomeningitis and Seoul viruses in an intercity population. Am J Trop Med Hyg 1991;44:117-21.

http://www.columbia.net/phys/barton.html
and
http://www.cdc.gov/ncidod/EID/vol1no4/barton.htm

by Linda Mueller-Anneling, Virus Serology Laboratory

Recently, the University Hygienic Laboratory in conjunction with the Centers for Disease Control and University of Iowa Hospitals and Clinics serologically detected a Lymphocytic Choriomeningitis (LCM) virus infection in a rural central Iowa infant.

LCM virus is a single stranded RNA virus in the arenavirus group and normally infects rodents.

House and field mice, guinea pigs, and hamsters may be inapparent carriers of the virus. Pet hamsters have been found to be a source of infection. Humans are only infected  incidentally through inhalation or ingestion of dust or food contaminated with virus present in the urine, feces, nasopharyngeal secretions, or blood of infected rodents. Human-to-human transmission of the virus has not been reported.

Human infection is considered to be rare, and is most prevalent in young adults. The incubation period is from six to thirteen days, but may be as long as three weeks. Three clinical forms of the disease, in addition to inapparent infections, occur: Aseptic meningitis, influenza-like or non-nervous system type, and meningoencephalomyelitis.

Infection with LCM virus is usually manifested as a nonspecific illness with fever, malaise, myalgia, retro-orbital headache, photophobia, anorexia, and nausea. The fever can last one to three weeks, and frequently may be biphasic. Neurological symptoms may vary from aseptic meningitis to severe encephalitis. Occasionally, arthritis, respiratory symptoms, orchitis, and blood cell depression may be present. Most clinically apparent LCM virus infections follow a benign course; very few fatal cases have been reported. However, congenital malformations may occur as a result of the infection of women with this virus during pregnancy.

LCM virus may be isolated from blood, cerebrospinal fluid, urine, or nasopharyngeal secretions. The method of choice is intracerebral inoculation of newborn mice. However, serological testing is more sensitive and is preferred over virus isolation for practical reasons. Serological diagnosis, either by complement fixation or ELISA, is accomplished by the detection of a four-fold rise in antibody titer between acute and convalescent phase sera. The virus isolation specimen and acute serum should be collected as soon as possible after onset of symptoms. A second, or convalescent serum, should be collected from 20 to 30 days after onset of symptoms. If negative, and the clinical symptoms are consistent with LCM infection, a third serum, collected at 45 to 80 days after onset may be submitted.

The UHL requests a patient history form be completed with requests for LCM testing. For additional information on specimen collection or transport, please contact the Virology and/or Virus Serology sections of the UHL at (319) 335-4500.

http://www.uhl.uiowa.edu/Publications/Hotline/1995All/lcmserological.html

Agent: Enveloped RNA virus, family Arenaviridae, genus Arenavirus

     Characteristics of Infection: Wild mice are the principal reservoir hosts, but laboratory animals  and humans are susceptible to the virus. Rodent infections are typically asymptomatic, but disease signs vary depending upon the virus strain, the mouse strain and the age of mouse at the time of infection. Only mice and hamsters readily transmit LCMV to other species, shedding virus in the urine, saliva and milk. ln mouse colonies, transmission is initially horizontal, but once infection is enzootic, the intrauterine route is used exclusively, and with near total efficiency.

     Public Health and Research Implications : LCMV infection can cause serious and rarely, fatal disease in people. LCMV has been found to contaminate biologic materials, including transplantable tumors; cell lines; virus stocks including leukemia, distemper, rabies and mouse poliomyelitis virus.

     Diagnosis: As natural rodent infections are generally asymptomatic and human infections result in nonspecific clinical signs, they are best diagnosed by virus isolation/ detection and serology.

     Specimens for virus isolation include blood, body fluids and tissues, especially kidney and urine when testing hamsters. Virus isolation should be performed on colonies that are seldom monitored and may be enzootically infected.

    Serology is most effective for routine monitoring of rodents and the diagnosis of LCMV in humans.  Methods include complement fixation (CF), neutralization test (NT), indirect immunofluorescence assay (IFA), radioimmunoassay (RIA), and ELISA . ELISA and IFA have replaced the less sensitive CF and NT. RIA is the most sensitive, but not routine.

     Eradication: The entire stock of animals should be destroyed and incinerated; cages and other equipment exposed to the animals should be autoclaved; the animal room should be fumigated with  formalin or paraformaldehyde and allowed to remain vacant for 7-10 days.

     If you would like further information about laboratory animal Health Monitoring programs, please call Charles River's Technical Assistance Department at 800-338-9680.

http://www.criver.com/pubs/sentinel/199801/win98.html

1.    Agent:

      An Arenavirus (Arenaviridae).  (The name comes from "arena," referring to"sand," from the electron microscopic appearance of the virions.  Related agents include Lassa, Machupo, and Junin hemorrhagic fever viruses.)

2.    Epizootiology:

      LCMV is important as a public health hazard.  LCM in persons usually is not a severe disease, but it can be serious.  All infected hamsters shed lots of virus in the urine, and it is readily transmitted.  In rodents it is transmitted transplacentally.

3.    Pathogenesis & pathology:

      The manifestations of LCM infection are dependent on genetically determined factors of both host and virus.  Genovesi and Peters (1987) report that PD4 and NHA inbred hamsters were highly susceptible, but CB and LSH hamsters were resistant. Other strains were intermediate in susceptibility.  The WE strain of virus was the most virulent, whereas the Armstrong strain was not virulent for hamsters of any strain, although the two virus strains were equally immunogenic.

      In experimental infections, most neonates and about half of young adults develop persistent viremia leading to immune complex glomerulopathy and vasculitis (panarteritis), with lymphocytic inflammatory lesions in the liver, kidney, lung, pancreas, spleen, meninges, and brain.  The other half of young adults and nearly all adults eventually clear the infection.  (LCM is a classic example of immune-mediated viral disease; immunosuppression decreases severity of lesions.)

4.    Diagnosis & control:

      Detectable by commercially available serologic tests.

5.    References:

Armstrong D et al. 1969. Meningitis due to lymphocytic choriomeningitis virus endemic in a hamster colony. J Am Med Assoc 209:265-266.

Baum SG et al. 1966. Epidemic nonmeningitic lymphocytic choriomeningitis virus
infection. New Engl J Med 274:934-936.

Biggar RJ et al. 1976. Implications, monitoring, and control of accidental transmission of lymphocytic choriomeningitis within hamster tumor cell lines. Cancer Res 36:537-553.

Biggar RJ et al. 1977. Lymphocytic choriomeningitis in laboratory personnel exposed to hamsters inadvertently infected with LCM virus. J Am Vet Med Assoc 171:829-833.

Bowen GS et al. 1975. Laboratory studies of a lymphocytic choriomeningitis virus
outbreak in man and laboratory animals.  Am J Epidemiol 102:233-240.

Genovesi EV, Peters CJ. 1987. Susceptibility of inbred Syrian golden hamsters
(Mesocricetus auratus) to lethal disease by lymphocytic choriomeningitis virus. Proc
Soc Exp Biol Med 185:250-261.

Gregg MB. 1975. Recent outbreaks of lymphocytic choriomeningitis in the United
States of America. Bull World Health Organization 52:549-553.

Hirsch MS et al. 1974. Lymphocytic choriomeningitis virus infection traced to a pet
hamster. New Engl J Med 291:610-612.

Hotchin J et al. 1974. Lymphocytic choriomeningitis in a hamster colony causes
infection in hospital personnel. Science 185:1173-1174.

Lewis AM Jr et al. 1965. Lymphocytic choriomeningitis virus in hamster tumors spread to hamsters and humans. Science 150:363-364.

Parker JC et al. 1976. Lymphocytic choriomeningitis infection in fetal, newborn, and
young adult Syrian hamsters. Infect Immun 13:967-981.

http://netvet.wustl.edu/species/hamsters/hamsters.txt

     To: promed-edr@usa.healthnet.org
     Subject: PROMED-EDR: LCMV & birth defects - USA
     From: "John P. Woodall" <woodall@wadsworth.org>
     Date: Sun, 19 Nov 1995 18:14:41 -0500 (EST)
     Reply-To: owner-promed-edr@usa.healthnet.org
     Sender: owner-promed-edr@usa.healthnet.org

Date: Sat, 18 Nov 1995 13:28:35 -0500
From: NeumannMA@aol.com

LYMPHOCYTIC CHORIOMENINGITIS VIRUS & BIRTH DEFECTS - USA
========================================================

The Oct-Dec 1995 issue of "Emerging Infectious Diseases" carried an article
by L.L. Barton describing the teratogenic associations of in utero
lymphocytic choriomeningitis virus (LCMV) infections.

In October, 1995, we saw a newborn infant with very advanced
chorioretinopathy and dramatic hydrocephalus.  His mother had experienced a
week long febrile illness during her fifth month of pregnancy which she
describes as one of very severe headaches causing her to remain in bed.
 There is no easily identified history of contact with rodents.

Pierre Rollin of the Special Pathogens Laboratory of the CDC was able to
identify elevated anti-LCMV IgG levels in the materal serum, infant serum and
infant CSF.  He also identified anti-LCMV IgM in the infant's CSF.

Attempts to demonstrate viral growth from CSF and urine using standard
clinical microbiological cell lines were negative.  VERO cells were not used.

The epidemiological study by J.E. Childs (Am. J. Trop. Med. Hyg. 1991; 41:
117-21) supports the notion that LCMV infections in humans may be more
prevalent than often suspected.  Perhaps LCMV will become a more recognized
member of the "Other" group in the TORCH w/u for congenital infections as
awareness for its presence increases.

I am aware of two other cases of probable LCMV infections associated with
congenital hydrocephalus which have been identified in the mid-West USA this
year.  I am interested in publicizing our case as a service for increasing
general awareness of this fairly novel problem.

I would certainly appreciate receiving news of other recent case
identifications or any other commentaries on this subject.

--
Mark Neumann, MD
Fellow in Pediatric Infectious Diseases
Wyler Hospital, University of Chicago.
NeumannMA@aol.com
............................................................................
http://www.healthnet.org/programs/promed-hma/9511/msg00096.html

          Virus Code. 03.0.1.1.001. Virus Accession number 03011001.
          Approved acronym: LCMV.

          Virus infects vertebrates.

          Description is on taxonomic level of species. Virus belongs to the serogroup or complex) LCM-LASV Complex (Old world arenaviruses).(VC 03.0.1.1. ); genus Arenavirus (VC 03.0.1. ); family Arenaviridae (VC 03. ).

Properties of Virion

     Morphology

Virions enveloped; slightly pleomorphic; spherical. Virions contain probably 2
nucleocapsid(s) per envelope. Virions (50-)110-130(-300) nm in diameter. Surface projections of envelope distinct; club-shaped (about 10 nm long); in small numbers dispersed evenly over all the surface. Host ribosomes seen inside the envelope (in varying numbers). Nucleocapsids filamentous (. isolated nucleocapsids, free of contaminating host ribosomes, are organised in closed circles and display a linear array of nucleosomal subunits); (450-)1000-1300 nm long; 9-15 nm in diameter. Symmetry helical.

Virions contain 2 % nucleic acid. Virions contain two segments of linear single stranded RNA.
Total genome length is 5000-7400 nt. Nucleotide sequence deposited at EMBL/GenBank under the following accession number LCM-ARM L: J04331; LCM-ARM M27693; LCM-ARM S: M20869; LCM-WE S: M22138. The largest segment 3400-4800 nt; of second largest 2400 nt. Nucleotide sequences of 3'-terminus largely complementary to similar regions on the 5' end; conserved nucleotide sequences; the same in species of same genus; S on RNA; 19-30 nucleotides long. Encapsidated nucleic acid both genomic and non-viral; including three
host ribosomal RNA. Genome found in one type of particle only. Each virion contains
often segments of genome not in equimolar proportions (due to frequent packaging of S
RNA strands).

          Virions contain 20 % lipid.

References

          The following references are cited in the Sixth ICTV Report: rf_arena.htm.

Data sources and contributors.

          The above description has been compiled from the data presented in the Sixth ICTV
          Report by Buchmeier MJ, Clegg JCS, Franze-Fernandez MT, Kolakofsky D, Peters
          CJ, Southern PJ.

http://www.res.bbsrc.ac.uk/mirror/auz/ICTVdB/03011001.htm#SymptHost

The natural host in the wild for the causative virus is the rodent population. Hamsters would most
likely acquire their infection from this source. Because hamsters are almost exclusively indoor pets,
they are unlikely to become infected with the virus. Hamster owners must, however, restrict contact
between their pets and orphaned wild rodents that have been adopted.
http://www.caringtogether.com/exotics/hamsters3.html#10

http://www.afip.org/vetpath/POLA/GUINEA_PIG.BUNTE.94

http://fiona.umsmed.edu/~yar/microhome/crab.html

          Molecular epidemiology of cytomegalovirus infections;
          Congenital viral infections, including CMV and lymphocytic choriomeningitis virus.

               Occupational risk of cytomegalovirus infection@ (NIH - R01)

          PENDING

               A Congenital lymphocytic choriomeningitis virus infection@ (MOD)
http://www-medlib.med.utah.edu/neuro/res_awards.html

MENINGITIS, VIRAL - ROMANIA
===========================
[see 960903151309]

Date: Wednesday, 4 Sep 1996 18:38:57 +0200

I would like to know if [lymphocytic choriomeningitis virus] LCMV has been
suspected and checked in these patients with viral meningitis in Romania.  If
not, I am ready to test this possibility.  I make LCMV diagnosis (IgM and IgG
ELISA, Ag-capture, western-blot, immunofluorescence, virus isolation on cells
or newborn mice) [BROUQUI, P., ROUSSEAU, M.C., SARON, M.F. and A. BOURGEADE.
Meningitis due to lymphocytic choriomeningitis virus in France. Clinical
Infectious Diseases, 1995, 20, 1082-1083] at the Pasteur Institute.

Furthermore, I'll be in Bucharest September 17-23 at the Cantacuzino
Institute and I would be happy to meet the clinicians and the representatives
of WHO and/or the Ministry of Health if they are interested in this
possibility and an eventual collaboration.

Thank you in advance for answering.

--
Dr M-F. SARON

Institut Pasteur
Unit d'Histopathologie
Laboratoire de Virologie Experimentale
28, rue du Dr Roux, 75724 PARIS CEDEX 15, FRANCE
TEL : 33-1-45-68-86-63
FAX : 33-1-40-61-33-23
e-mail: mfsaron@pasteur.fr

[Mod. Were the Romanian cases due to LCMV it would indeed be a very large
epidemic of this virus.  I know of no "outbreaks" of LCMV approaching this
Romanian experience of "281 cases of suspected viral meningitis" within one
month.  Most cases of LCM are sporadic, as I recall.]
........................................................................chc
http://www.healthnet.org/programs/promed-hma/9609/msg00015.html

I. Background

A. Terminology. Subarachnoid inflammation from any cause other than pyogenic bacteria or fungi. The differential includes viruses, other microorganisms, and non-infectious causes viral meningitis. Since most cases are caused by viruses, the terms "aseptic" and "viral" are often used synonymously.

     Viral Diseases with Systemic Manifestations

     mumps
     herpes simplex
     varicella-zoster
     adenoviruses
     Epstein-Barr virus
     parvovirus (erythema infectiosum)
     lymphocytic choriomeningitis virus

     partially treated bacterial
     parameningeal infection
     mastoiditis
     sinusitis
     brain abscess
     spirochetal infections
     syphilis
     leptospirosis
     Lyme disease
     fungal
     cryptococcal
     coccidioidomycosis
     histoplasmosis
     tuberculous
     toxoplasmosis
     Rocky Mountain Spotted Fever
     Mycoplasma pneumoniae
     Bartonella henselae (cat scratch disease)
     amebic meningoencephalitis

     brain tumor
     carcinomatous
     chemical
     intrathecal drugs and radiographic dyes
     lead poisoning
     benign intracranial hypertension

     Kawasaki disease

B. Etiology

1. may occur as part of a broader range of clinical manifestations caused by some viruses (Table 1 ).

2. The differential diagnosis where is the sole or dominant manifestation is more limited (Table 2).

a. Prior to the discovery of the non-polio enteroviruses (circa 1950), most cases were considered to be "non-paralytic" poliomyelitis.

b. Large studies conducted from 1955 to 1962 among patients of all ages (1-3), found multiple agents caused. Mumps virus and poliovirus infections are now controlled by immunization in the U.S.

     Diseases Limited to Central Nervous System

     enteroviruses
     mumps
     arboviruses
     lymphocytic choriomeningitis virus (LCM)

Unknown Etiology

     Mollaret's syndrome
C. A prospective study conducted at three Baltimore hospitals from 1986 to 1990 showed > 90% of viruses isolated from children under 2 y/o are coxsackie B viruses and echoviruses; coxsackie A viruses appear to cause < 3% of cases (4).

A. Seasonality. disease activity corresponds to the seasonal pattern observed with all enterovirus infections, i.e., a marked summer-fall predominance. Disease occurs at a lower incidence at other times of the year.

B. Rates of Disease

1. Based on continuous surveillance in Olmsted County, MN the overall population-based rate of physician-diagnosed was 17.8 per 100,000 person-years from 1976 through 1981 (5). This rate compares closely with the 17.8 cases per 100,000 persons under 20 years of age discharged from Maryland hospitals from 1979 through 1983 (Unpublished Data, Hospital Services Cost Review Commission, State of Maryland, 1984) and is similar to a two-year survey in Israel which found a rate of 21.6 per 100,000 person-years (6).

2. The age-specific incidence has varied somewhat among different reported outbreaks (7-14), but most data indicate that is predominantly a disease of infants less than a year of age. A declining number of cases are recognized among persons within increasingly older age groups (7,10). These data are likely to contain some case-ascertainment bias; i.e., febrile infants are more likely to have lumbar punctures than older children and adults.

     A. Clinical Presentation

1. In the older child and adult presents with fever to 400 C, headache, meningismus, nausea and vomiting (10). Other signs of enterovirus infection, i.e., rash, are present in a minority

enzootic

Main Entry: en·zo·ot·ic
of animal diseases : peculiar to or constantly present in a locality

Main Entry: vi·re·mia
: the presence of virus in the blood of a host

Main Entry: zoo·no·sis
: a disease communicable from animals to humans under natural conditions