The Topic of This Month Vol.23 No.8(No.270)

The trend of enterovirus isolation in association with aseptic meningitis, 1999-2002

(IASR 2002; 23:193-194)

In Japan, epidemics of aseptic meningitis occur every summer; the etiological agents are mainly such enteroviruses as echoviruses (E), group B coxsackieviruses (CB), and other viruses (see IASR, Vol. 21, No. 10). The prevailing enterovirus serotypes change from year to year as well as from area to area. The prognoses of meningitis due to enteroviruses are basically good. In rare occasions, acute encephalitis may develop and isolation of enterovirus 71 (EV71) from severe or fatal cases has been reported (see IASR, Vol. 19, No. 3 and Vol. 22, No. 6). In 1997-1998, nationwide epidemics with E30 infection occurred (see IASR, Vol. 19, No. 8); the number of aseptic meningitis patients reported in 1998 counted at 5,780 (15.66 per sentinel among 369 sentinels), the second largest number ever reported after 7,672 patients (14.05 per sentinel among 546 sentinels) in 1991 (see IASR, Vol.13, No.8) in the previous National Epidemiological Surveillance.

In the new National Epidemiological Surveillance of Infectious Diseases (NESID) in compliance with the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections enacted in April 1999, about 470 sentinel hospitals report weekly aseptic meningitis patients having been diagnosed clinically (in the former system until March 1999, the reports were monthly). Prefectural and municipal public health institutes (PHIs) attempt isolation and typing of aseptic meningitis etiological viruses from specimens (cerebrospinal fluid, stools, and pharyngeal swabs) collected at sentinels for infectious agent surveillance. The positive results are reported. The current article deals with the incidence of aseptic meningitis during 1999-2002 and the recent enteroviruses associated with meningitis.

Incidence: The number of aseptic meningitis patients reported in 1999 (April-December) was rather small, being 1,126 (2.47 per sentinel), and it was 1,873 (4.08 per sentinel) in 2000 and 1,246 (2.67 per sentinel) in 2001. The number of patients has suddenly increased since the 19th week of 2002 (Fig. 1). The cumulative number of patients from the 1st through 29th weeks counted at 1,548 (3.29 per sentinel), largely outnumbering the figures reported during the same period of the past three years. In Fukui prefecture and prefectures in western Japan, such as Okayama, Kochi, and Kumamoto, a large number of patients per sentinel were reported (Fig. 2).

Isolation of enteroviruses: The viruses isolated from aseptic meningitis patients every year during 1999-2002 are shown in Fig. 3. In 1999, E6, CB5 and E17 were isolated frequently, so were E11, EV71, E25 and E9 in 2000, and E11 and CB5 in 2001. Each type of echoviruses and EV71 have tended to be prevalent with intervals of several to 10s of years (, while all types of CB2-5 are isolated every year (

After May 2002, reports of aseptic meningitis patients and those of virus isolation are both on the increase (Fig. 4). Those of echoviruses numbered at 467 (33 of E9, 179 of E11, 225 of E13, and 19 of E30) (number of reports as of July 24) (Fig. 3). Reports of isolation of E9 have been on the increase from Kochi prefecture (see p. 197 of this issue). Those of E11 have been on the increase in Kagawa prefecture and those of E30 in Okayama (see p. 195 of this issue) and Hiroshima prefectures (see p. 196 of this issue) (Fig. 5).

E13 was isolated only once in Gifu prefecture during the Infectious Agents Surveillance by the Ministry of Health and Welfare Research Group in 1980 and it had not been isolated until the 34th week of 2001. After isolation in Wakayama, Fukui, and Fukushima prefectures and Osaka city in 2001 (see IASR Vol. 22, No. 12, and Vol. 23, No.5), isolation one after another could be seen in many districts in 2002 (see IASR, Vol. 23, No. 7 and p. 195-196 of this issue) and reports of isolation have come out from 28 PHIs in 24 prefectures. A 99% homology was shown in the nucleotide sequence in the VP1 region between the strains isolated in Hiroshima prefecture in 2002 and that in Fukushima prefecture in 2001 (see p. 196 of this issue). Since there have been no epidemics for a long time and not many people are immune to E13 (see IASR, Vol. 23, No. 7 and p. 196 of this issue), epidemics may further spread to the whole country.

E9 and E11 were isolated mostly from the young, of which aseptic meningitis patients with E9 peaked at the age of 5 years and those with E11 at the ages of 0 year and 4-5 years (Fig. 6). In contrast, E13 was isolated from a wide range of ages, and meningitis patients were distributed among those at the ages of 0 year and more than 3 years. From other than aseptic meningitis patients, isolation of E9 is frequent from cases with exanthemas and that of E11 from cases with upper respiratory illness.

In identification of E13, one must be aware that the echovirus typing antiserum panel "EP95" (see IASR, Vol. 18, No. 3) does not contain E13, but it could be identified with commercially available monovalent antiserum or Schmidt pool antiserum panel.

Although E13 had seldom been isolated in foreign countries, isolation increased in European countries, such as England and Wales and Germany in 2000-2001 and in Australia and USA in 2001, causing meningitis epidemics (Eurosurveillance Weekly, No. 7, 2002 and CDC, MMWR, Vol. 50, No. 36).

Since no specific control measures of aseptic meningitis are known, as a general method of preventing enterovirus infection, fundamental good hygiene practice, particularly thorough hand washing (after defecation or diaper exchange) is important. When such symptoms as fever, headache, vomiting, splenetic (ill temper in infants) appear after those of summer cold, it is recommended to visit immediately a nearby medical institution for diagnosis.

The Infectious Disease Surveillance Center, the National Institute of Infectious Diseases has uploaded the most recent trend of incidence and virus isolation on the following URLs ( and to provide information to physicians in charge of patient diagnosis and to all organizations concerned.

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