Role of the virology laboratory in diagnosis and management of ...

CLINICAL MICROBIOLOGY REVIEWS, Jan. 1989,

p.

Vol. 2, No. 1

1-14

0893-8512/89/010001-14$02.00/0 Copyright © 1989, American Society for Microbiology

Role of the Virology Laboratory in Diagnosis and Management of Patients with Central Nervous System Disease TASNEE CHONMAITREE,l2* CONSTANCE D. BALDWIN,' AND HELEN L. LUCIA'2 Departments of Pediatrics' and Pathology,2 University of Texas Medical Branch at Galveston, Galveston, Texas 77550 INTRODUCTION ......................................................................1 CNS DISEASES CAUSED BY VIRUSES .....................................................................2 Enteroviruses ......................................................................2 Normal host ......................................................................2 Compromised host ......................................................................3 4 Togaviruses, Bunyaviruses, and Reoviruses ...................................................................... Herpesviruses ......................................................................4 4 HSV ....................................................................

VzV ....................................................................

4

4 EBV .................................................................... CMV ......................................................................4 Mumps, Measles, and Rubella ......................................................................5 Lymphocytic Choriomeningitis Virus ......................................................................5 5 Rabies ..................................................................... HIV ......................................................................5 DIAGNOSTIC METHODS FOR ENTEROVIRUSES ......................................................................5

Rapid Diagnosis ......................................................................5 Isolation of Virus ......................................................................6 Specimen collection and transport ......................................................................6 Cell culture ......................................................................6 Animal inoculation ......................................................................7 Identification of isolates ......................................................................7 Serology ......................................................................7 DIAGNOSTIC METHODS FOR NONENTEROVIRUSES ................................................................7 7 Togaviruses, Bunyaviruses, and Reoviruses ...................................................................... Herpesviruses ......................................................................8 Mumps, Measles, and Rubella .......................................................................8 Lymphocytic Choriomeningitis Virus .......................................................................8 8 Rabies ...................................................................... HIV .......................................................................8 MANAGEMENT OF PATIENTS WITH CNS VIRAL INFECTION ...................................................9 Aseptic Meningitis .......................................................................9 Meningoencephalitis .......................................................................9 Enteroviral Meningoencephalitis Associated with Agammaglobulinemia ............................................9 INFLUENCE OF THE VIROLOGY LABORATORY ON PATIENT MANAGEMENT ..........................9 CONCLUSION ...................................................................... 10 ACKNOWLEDGMENTS ...................................................................... 11 LITERATURE CITED ...................................................................... 11

useful for patient care, costs were high, and collection and transport of specimens were difficult. Physicians were more likely to use a viral laboratory if it was located within their institution. The discovery of many types of antiviral therapy has mandated the establishment of more accessible facilities for viral diagnosis and development of more rapid diagnostic techniques. At present, increasing numbers of diagnostic facilities are becoming available at university medical centers, Veterans Administration hospitals, and even some community hospitals (81, 98, 110, 128). In addition, some central laboratories have reached out to offer viral diagnostic facilities to the surrounding community (124, 128). These laboratories vary in size and emphasis on diagnostic methods. The laboratory can now operate on a modest scale, be tailored to the needs of the patients it serves, and provide

INTRODUCTION

Before antiviral therapy became available, viral diagnosis clinically primarily to identify a community outbreak of viral disease and to provide prognostic information to the patient. The delayed reports of viral culture results dictated that diagnostic information was generally not available until the patient's illness was over. Because demand for the technology was limited, diagnostic virology facilities were, until recently, available only in reference laboratories and some university hospitals. In a survey published 12 years ago, only 60% of 115 U.S. medical centers reported on-site viral diagnosis (60). Physicians avoided using these laboratories because results were delayed and often not was used

*

Corresponding author. 1

2

CLIN. MICROBIOL. REV.

CHONMAITREE ET AL. TABLE 1. Recognized human enterovirus serotypes Types Virus

1-3 Polioviruses .................... Group A coxsackieviruses'.................... 1-24 1-6 Group B coxsackieviruses .................... Echoviruses".................... 1-34 Enteroviruses'.................... 68-72 Type 23 is the same as echovirus 9. Type 10 is reclassified as a reovirus: type 28 is a rhinovirus. EnteroviruLs type 72 is hepatitis A virus.

important information for patient management (81, 94, 157). This article reviews acute central nervous system (CNS) diseases caused by viruses and the usefulness of the virology laboratory in diagnosis and management of patients with these diseases. The more common enteroviral diseases are emphasized. CNS DISEASES CAUSED BY VIRUSES Viral infections of the CNS have two major clinical presentations: aseptic meningitis, which is by far the most frequent, and viral meningoencephalitis. The enteroviruses cause most acute viral infections of the CNS (35 to 83%). with mumps a distant second (1 to 40%), worldwide (9, 20, 42, 44, 116, 146). Herpesviruses, togaviruses. bunyaviruses. lymphocytic choriomeningitis virus, and measles and rubella viruses can also cause CNS disease. More recently. the role of human immunodeficiency virus (HIV) in the etiology of CNS disease has been recognized (48). Enteroviruses Enteroviruses constitute a genus of the Picornaviridae family which currently includes 69 serotypes made up of

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Co o %I-

polioviruses, coxsackieviruses, echoviruses, and enterovirus types 68 to 72 (Table 1). This review will exclude from the discussion of enteroviral diseases poliomyelitis and other diseases caused by the three types of polioviruses. Enteroviruses have a worldwide distribution, with increased prevalence in temperate climates during the warm months of the year (54, 102. 103. 115). A recent survey from the Centers for Disease Control showed that the temporal pattern of isolation of nonpolio enteroviruses differs among regions of the United States. However, a mean of 84% and a range of 65 to 93%c of virus isolations in a region were made between July and January (143). Figure 1 shows the seasonal prevalence of enteroviruses isolated in the Clinical Virology Laboratory of The University of Texas Medical Branch (UTMB) in Galveston, Tex., from 1983 to 1987. Although outbreaks of disease associated with a single serotype of enteroviruses are often reported (12. 29, 72, 144), the far more common pattern is endemic infection caused by several enterovirus types (28, 107. 157). The predominant types may vary yearly and may vary by locality even within the same year. Normal host. Enteroviral diseases in normal hosts are most often seen in young infants and children (54). Enteroviruses are mainly spread by the fecal-oral route. The incubation period ranges from 1 day to 3 weeks but is generally 3 to 5 days. CNS disease is a common manifestation of infections caused by a variety of nonpolio enteroviruses, with aseptic meningitis being the most common. Less common diseases include encephalitis, paralysis, GuillainBarre syndrome, cerebellar ataxia, and peripheral neuritis (10, 26, 29, 41-43. 54. 69, 133). CNS disease sometimes occurs as a part of disseminated enteroviral infection, with viremia and involvement of heart, liver, kidneys, adrenal glands, and the blood coagulation system (14, 26, 56, 71, 75, 77).

150 140130120 110-

100 90 80 70-

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6 E 50Z 40 30M~~~~~~Mnh 20-

10 Jan.

Feb. Mar. Apr. May June July Aug. Sept. Oct. Nov. Dec.

Months FIG. 1. Seasonal prevalence of enteroviruses as represented by number of enteroviruses (including polioviruses) isolated by month from clinical specimens submitted to the Clinical Virology Laboratory. UTMB. 1983 to 1987. In two separate outbreaks in 1984. echoviruses 9 (April to July) and 11 (September to December) predominated.

VOL. 2, 1989

THE VIROLOGY LABORATORY AND DIAGNOSIS OF CNS DISEASE

TABLE 2. Age distribution of 103 children with enteroviral meningitis diagnosed at UTMB, 1983 to 1987" Age group

No. of cases

Cumulative %

6 yr

20 31 20 18 14

19 50 69 86 100

" All had an enterovirus in the CSF. Data were collected by Cheryl Banks.

Approximately 3,200 to 12,700 cases of aseptic meningitis were reported annually to the Centers for Disease Control between 1973 and 1983 (24), but its actual incidence is probably severalfold higher. Enteroviruses account for the majority of the identified agents causing aseptic meningitis, and yearly peak occurrences of the disease closely coincide with periods of most frequent enterovirus isolation (20, 24). Enteroviral aseptic meningitis caused by numerous types of coxsackieviruses, echoviruses, and enterovirus 71 (26, 29) occurs in both epidemics and isolated cases. In general, enteroviral meningitis is more common in young patients, especially those under 1 year of age. Age ranges of 103 children with enteroviral meningitis diagnosed at UTMB from 1983 to 1987 are shown in Table 2. Clinical signs and symptoms of enteroviral CNS disease in young children are mostly nonspecific and mimic those of bacterial sepsis or meningitis or both. Onset of illness can be abrupt or gradual. Fever is the most common presenting symptom, followed by irritability, lethargy, anorexia, gastrointestinal or respiratory symptoms or both, otitis media, and rash (15, 36, 137, 157, 160). In one study, apnea occurred in 9% of children with enteroviral meningitis (157). Specific signs and symptoms of CNS disease, such as nuchal rigidity and bulging fontanelle, may or may not be present. Seizures occur in