Aseptic meningitis

Aseptic or viral meningitis is the most common type o1 meningitis and is associated with an estimated 26,000-42,000 hospitalizations each year in the United States (1). Enteroviruses are the most common cause of aseptic meningitis (2). Echovirus 9 (E9) and echovirus 30 (E30) have been associated frequently with outbreaks of aseptic meningitis (3-5). During March 2003, several state public health departments noted increased reports of aseptic meningitis and, as of August 7, seven states (Arizona, California, Georgia, Idaho, Oregon, South Carolina, and Texas) had reported outbreaks associated with either E9 or E30. This report summarizes the epidemiologic features of the aseptic meningitis outbreaks in five states (Arizona, California, Georgia, Idaho, and South Carolina) and provides an overview of enterovirus activity in the United States during January 1-August 7. Enteroviruses, E9 and E30 in particular, should be considered in the differential diagnosis of persons with aseptic meningitis.

Aseptic meningitis is not a nationally notifiable disease, and no nationally accepted case definition exists for this condition (6). Therefore, cases of aseptic meningitis described in this report represent physician diagnoses based on clinical presentation and laboratory findings. The enterovirus surveillance data were obtained from reports to the National Enterovirus Surveillance System (NESS), a passive voluntary surveillance system based on reporting by state public health and private laboratories of enterovirus detections by serotype and basic demographic information, specimen type, and date of collection.

Aseptic Meningitis Outbreaks

Arizona. During January 1-July 31, a total of 465 cases of aseptic meningitis (rate: 8.6 per 100,000 population) were reported to the Arizona Department of Health Services, compared with 104 cases (rate: 1.9) reported for the same period in 2002. The highest rate during January 1-July 31 was reported in Maricopa County (rate: 12.7, compared with 2.7 during the same period in 2002). As of July 31, the Arizona State Health Laboratory had reported 62 enterovirus isolates, the majority (66%) from cerebrospinal fluid (CSF) specimens. Of the 62 isolates, E30 accounted for 47 (76%) isolates and E9 for one (2%) isolate.

California. As of August 5, a total of 1,753 cases of aseptic meningitis (rate: 8.0 per 100,000 population) had been reported to the California Department of Health Services (CDHS). During 1999-2003, the annual reported rate of aseptic meningitis in California ranged from 4.5 to 7.3. Specimens from 148 patients with aseptic meningitis were submitted to CDHS for diagnostic testing from 24 counties throughout the state (Table). Serum and CSF specimens from all patients were tested for enteroviruses and arboviruses (i.e., West Nile virus [WNV], St. Louis encephalitis, and western equine encephalitis) at CDHS. Of the 148 patients, 82 (55%) had evidence of enterovirus infection by polymerase chain reaction (PCR) or culture; E30 was identified from 29 (85%) of the 82 culture-positive cases, and E9 was identified from four (12%) cases.

Georgia. During March, an outbreak of aseptic meningitis associated with E9 infection began in Augusta, Georgia. During March 10-July 23, a total of 320 cases were reported from 50 of Georgia's 159 counties, compared with 227 cases reported statewide during 2002. E9 has been isolated from CSF, throat swab, and/or rectal swab specimens of 24 patients. Enteroviruses (untyped) were isolated from an additional 24 CSF specimens, and 52 CSF specimens tested positive for enteroviruses by PCR. Patients commonly reported headache, fever, nausea or vomiting, stiff neck, and photophobia (Table). As of August 7, the outbreak was ongoing.

Idaho. During May 21-July 17, an outbreak of viral meningitis occurred in north central Idaho, with 38 cases from three adjacent counties reported to the Idaho Division of Health, compared with four cases reported statewide during the previous year. Of the 32 patients for whom clinical information was available, 17 (53%) were hospitalized with clinical signs and symptoms consistent with aseptic meningitis (Table). E30 was isolated from two of four patients who underwent virologic investigation. Two cases of aseptic meningitis reported subsequently from the same area are under investigation by the North Central District Health Department.

South Carolina. During April 6-July 31, a total of 82 cases of viral meningitis were identified by the Aiken County Health Department. The outbreak peaked during May, when 38 cases were reported. E9 was isolated from CSF of two of these patients. At the same time, adjacent counties in Georgia also experienced an outbreak of aseptic meningitis associated with E9. In June, cases began to appear in multiple counties. The number of reports and CSF specimen submissions to the South Carolina State Laboratory continued to increase in July. As of July 31, a total of 130 cases of aseptic meningitis had been reported; E9 was isolated from 20 specimens (18 CSF and two throat washings) from eight different counties, and no other enteroviruses were identified. Because viral meningitis is not a notifiable disease in South Carolina, comparative data are not available for previous years.

Enterovirus Surveillance Data

As of August 7, NESS had received reports of 365 enterovirus detections in 25 states; source specimens for these isolates were collected during January 5-July 30. The most commonly detected serotypes were E9 and E30, with E30 accounting for 132 (36%) and E9 accounting for 108 (30%) reports. E9 was isolated in 14 states, predominantly in the East (e.g., Georgia, Florida, New Jersey, and South Carolina), and E30 was isolated in 10 states, predominantly in the West (e.g., Arizona, California, Colorado, and Texas). For both serotypes, CSF was the source specimen in the majority of cases (72 [67%] for E9 and 107 [81%] for E30).

Other enterovirus serotypes reported most frequently include coxsackievirus B1 (29 [8%] of all reports), echovirus 7 (10 [3%]), coxsackievirus A9 (10 [3%]), enterovirus 71 (nine [3%]), coxsackievirus B4 (12 [4%]), and echovirus 5 (seven [2%]).

Editorial Note: Aseptic meningitis is a central nervous system infection characterized by fever and meningeal symptoms with moderate, predominantly lymphocytic CSF pleocytosis and the absence of bacterial pathogens in CSF. The disease occurs both sporadically and in outbreaks, and >90% of cases with an identified cause are associated with enteroviruses (2). Many aseptic meningitis outbreaks occurring during the current enterovirus season reflect high levels of E9 and E30 activity. In 2003, E9 has been involved predominantly in the outbreaks in the East, and E30 has been linked exclusively with outbreaks in the West.

During 1970-2001, both E9 and E30 were among the 15 enteroviruses reported most commonly each year, accounting for 10.2% and 8.2% of all enterovirus isolates reported to CDC, respectively (CDC, unpublished data, 2003). However, these enteroviruses have been relatively quiescent in recent years; E9 has not been the predominant enterovirus isolated from clinical specimens since 1995, and E30 has not been widespread since 1998 (7,8). This probably has resulted in an accumulation of cohorts of susceptible persons who have not been exposed previously to these agents. The increase in aseptic meningitis cases associated with high activity of E9 and E30 is consistent with the historic data; during 1988-1999, peak years for viral meningitis hospitalizations in the United States coincided with periods of high activity of either E9 or E30 (1).

Although the majority of cases of enterovirus infections are asymptomatic or result in mild febrile illnesses, aseptic meningitis is the predominant diagnosis reported with the current E9 and E30 activity in the United States because patients with meningitis are more likely to be tested for enteroviruses than those with less severe manifestations. In a small proportion of cases, more severe, life-threatening diseases (e.g., encephalitis, paralysis, myopericarditis, and neonatal enteroviral sepsis) might occur.

Enteroviruses typically demonstrate a marked seasonality in temperate climates, with a typical enterovirus season in the United States occurring during June-October (9). In 2003, the enterovirus season appears to have started early, with the first isolations of E9 reported in January (in Louisiana), the first outbreaks of E9-associated aseptic meningitis reported in March, and the first isolations of E30 reported in April (in Arizona).

WNV has the same seasonal pattern as enteroviruses, and is also associated with neurologic signs and symptoms of aseptic meningitis. However, WNV-associated meningitis tends to occur among older persons (median age: 46 years) (10), whereas children and young adults (median age: 13 years) are at highest risk for enteroviral meningitis (1). The investigation of an aseptic meningitis outbreak in an area of high WNV epizootic activity in 2001 indicated that enteroviruses were the leading cause of aseptic meningitis in this area, and no evidence of WNV infection was detected (10). For this reason, diagnostic testing of specimens from younger patients with aseptic meningitis should include testing for enteroviruses, even during a documented WNV outbreak (10).

Early etiologic diagnosis of aseptic meningitis helps to avoid unnecessary antibiotic treatment and additional testing. Although virus culture is the standard technique for enterovirus detection, it consumes time and resources and has limited clinical use. Molecular methods of enterovirus detection (e.g., PCR and typing based on genomic sequences) are increasingly becoming available. Serotype-specific PCR primers have been developed by CDC for several enteroviruses, including E30 (5). These serotype-specific primers are useful for rapid differentiation of cases in patients infected with the outbreak strain from sporadic infections with other enteroviruses.

Aseptic meningitis is a benign, self-limiting illness, and severe illness and death are uncommon. The treatment is symptomatic and the majority of patients recover in approximately 1 week. Enteroviruses typically are spread person to person through the fecal-oral or oral-oral routes and through respiratory droplets and fomites. No specific prevention or control measures are available for nonpolio enteroviruses including E9 and E30. Adherence to good hygienic practices, such as frequent and thorough hand washing (especially after diaper changes), disinfection of contaminated surfaces by household cleaners (e.g., diluted bleach solution), and avoidance of shared utensils and drinking containers, are recommended to help interrupt transmission.

Acknowledgments

The findings in this report are based on data contributed by W Zakowicz, C Levy, MS, K Komatsu, MPH, A Bernstein, MS, G Briggs, MS, L Erhart, MPH, R Schofield, M Fink, MS, Arizona Dept of Health Svcs. A Diggs, MPH, A Wood, MPH, A Edmonds, C Holloway, Jr, J Carlson, MS, J Sollenberger, MS, R Klein, S Santana, MPH, V Berisha, MD, Maricopa County Dept of Public Health, Phoenix, Arizona. D Schnurr, PhD, California Dept of Health Svcs. RT Morales, MPH, Georgia Div of Public Health. V Runick, Aiken County Health Dept, Aiken; M Tolson, South Carolina Dept of Health and Environmental Control. L Rogers, D Anderson, North Central District Health Dept, Lewiston, Idaho. J Langer, ARUP Laboratories, Salt Lake City, Utah. W Nix, S Oberste, PhD, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

References

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(2.) Rotbart HA. Viral meningitis. Semin Neurol 2000;20:277-92.

(3.) Uysal G, Ozkaya E, Gwen A. Echovirus 30 outbreak of aseptic meningitis in Turkey. Pediatr Infect Dis J 2000;19:490.

(4.) CDC. Outbreak of aseptic meningitis--Whiteside County, Illinois, 1995. MMWR 1995;46:221-4.

(5.) CDC. Summary of notifiable diseases, United States, 1994. MMWR 1995;43:1-8.

(6.) Kilpatrick DR, Quay J, Pallansch MA, Oberste MS. Type-specific detection of echovirus 30 isolates using degenerate reverse transcriptase PCR primers. J Clin Micro 2001;39:1299-302.

(7.) CDC. Nonpolio enterovirus surveillance--United States, 1993-1996. MMWR 1997;46:748-50.

(8.) CDC. Enterovirus surveillance United States, 1997-1999. MMWR 2000;49:913-6.

(9.) Strikas RA, Anderson LJ, Parker RA. Temporal and geographic patterns of isolates of nonpolio enterovirus in the United States, 1970-1983. J Infect Dis 1986;153:346-51.

(10.) Julian KG, Mullins JA, Olin A, et al. Aseptic meningitis epidemic during West Nile virus avian epizootic. Emerg Infect Dis (in press).

R Cheshier, Arizona Dept of Health Svcs. E Tu, C Glaser, MD, California Dept of Health Svcs. K Bryant, MPH, K Arnold, MD, Georgia Div of Public Health. K Carter, DVM, Idaho Div of Health. E Brenner, MD, South Carolina Dept of Health and Environmental Control. SP Montgomery, DVM, Div of Vector-Borne Infectious Diseases; A LaMonte, MPH, N Khetsuriani, MD, M Pallansch, PhD, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

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