The Topic of This Month Vol.21 No.1(No.239)
Rubella is a viral exanthematous disease affecting principally children, generally of a mild nature, and its epidemics emerge from spring to early summer in Japan. If a woman is infected during an early stage of pregnancy and the fetus is infected transplacentally, rubella may sometimes be accompanied with congenital rubella syndrome (CRS) characterized by hearing loss, cataract, and heart defect. Therefore, surveillance and countermeasures for rubella are undertaken on the primary standpoint of preventing CRS. Vaccination has been ruled by the amended Preventive Vaccination Law enforced on April 1, 1995 to change from the former mandatory mass inoculation to individual inoculation upon recommendation. Routine immunization against rubella has continuously been applied, but the target has been changed from "girls at the ages of 13 to 15 years" to "children of both sexes aged >=12 months through <90 months" (hereafter referred to as merely "young children"). In the new Infectious Diseases Control Law enacted since April 1, 1999, rubella has been placed as one of the category IV infectious diseases to be reported by the pediatric sentinels and CRS as that to be notified by all physicians (see IASR, Vol. 20, No. 4).
Rubella patients: According to the incidence of rubella reported by the sentinel clinics conforming to the National Epidemiological Surveillance of Infectious Diseases (NESID) (Fig. 1), nationwide large-scale epidemics recurred almost every 5 years; in 1982, when NESID started, 1987-88, and 1992-93. Since 1994, however, no such a large-scale epidemic has occurred but there have been only localized or small-scale ones (Fig. 2). Patients per sentinel clinic (about 2,400 in the whole country) counted at the largest number in 1987, when a large-scale outbreak occurred. Since 1994, small-scale epidemics have occurred every year; particularly, 1999 ended up with the fewest cases ever reported (Table 1).
CRS patients: Since April 1 (as of December 15), 1999, no single CRS patient has been reported under the Infectious Diseases Control Law. The questionnaires sent to schools for the aurally handicapped (Kadoya et al., Clinical Virology, 23, 141-147, 1995) and to hospitals (Katow, Clinical Virology, 23, 148-154, 1995) in 1993 were the last nationwide surveys for CRS patients. The former found out 639 cases during 1963-92 and the latter 301 cases during 1978-93. After then, a few CRS cases were reported in association with the localized rubella epidemics in Hokkaido and elsewhere (see p. 7 of this issue). Since 1994, when rubella cases began to decrease, CRS cases may also have been decreasing.
Dendrogram of epidemic virus strains: If 25 strains of rubella virus isolated during 1966-97 are compared in the 1,441 bases of the nucleotide sequences encoding E1 protein possessing a hemagglutinating activity, the strains isolated during each epidemic period are found to form a cluster on the dendrogram. This indicates that the prevailing virus strain alternates whenever a nationwide epidemic occurs (Sanogo et al., 47th Cong. Jpn. Soc. Virol., 1999). Even so, since there is little change in the antigenicity, the today's vaccine strain might not cause any problem in its efficacy.
Target ages of routine immunization and the vaccination coverage: In compliance with the amended Preventive Vaccination Law, rubella vaccine has been given to young children aged >=12 months through <=36 months as a standard schedule. As interim measures for those who have never received rubella monovalent vaccine nor measles-mumps-rubella trivalent (MMR) vaccine, the target of routine immunization will be 1) both boys and girls who were in the 1st or 2nd grade of elementary school in 1995, 2) those who were in the 1st grade of elementary school during 1996-1999, and 3) those aged 12 through 15 years before the 16th birthday (preferably when in junior high school) by September 2003. It has been pointed out that the vaccination coverage of female junior high school students has decreased after amendment of the Law. According to the survey conducted by Isomura (see p. 3 of this issue), the actual coverage was 60% of young children and 46% of junior high school students in 1997. If the vaccination coverage of junior high school students is compared between free individual versus free mass vaccination groups, the former is 28% and the latter 71% with a big difference.
Antibody prevalence: According to the National Epidemiological Surveillance of Vaccine-Preventable Diseases (NESVPD) in 1997, more than 90% of females at the ages of 17-32 years had the antibody. In contrast, the antibody prevalence in males of the same ages stood at about 70%. These results point out a high efficacy of vaccination of female junior high school students that has been continued since 1977 (Fig. 3). Two peaks of antibody prevalence were seen at 2-4 years and 7-10 years of age among boys and girls aged less than 10 years. The first peak corresponds to the young children who received the vaccination by the standard schedule after amendment of the Law, and the second one to the children who received MMR only during April 1989-March 1993 or single rubella vaccine at elementary school age after the amendment came out. All these results demonstrate acquisition of antibody by vaccination. The antibody prevalence of those aged 11-14 years was as low as 50-79%. It is desirable that those who were at these ages at the time of the 1997 survey will acquire the immunity by vaccination (voluntary vaccination is recommended even if aged over the target ages). The geometric mean titer of antibody positives, which is an indicator of the immune level of a population, is being kept sufficiently high at over 1:26 (1:64) in both males and females until their 10s-30s (Fig. 4).
Discussion: The reason why no large-scale outbreak occurred since 1994 may be that young children, the main constituency of epidemics, were immunized with MMR vaccine during 1989-1993 and have been immunized with single rubella vaccine since April 1995. If vaccination is more promoted and maintained, it is anticipated that nationwide large-scale epidemics would not occur in the future.
In Greece, such a low coverage of rubella vaccination among children as 50% or lower kept on during the mid-1970s toward 1987, and antibody negatives (susceptibles) among pregnant women increased from 11% in 1980 to 36% in 1990-91. Rubella infection increased among young adults including pregnant women due to the rubella epidemics in 1993 and 25 cases of CRS occurred during July 1993-June 1994 (BMJ, 319, 1462-1467, 1999). To avoid similar problems in Japan, it is important to strive to improve the vaccine coverage, being low at present, and to keep the trend of high vaccine coverage.
Due to the reduced scales of epidemics, it seems possible that no boosting of immunity can be expected by reinfection with wild-type virus (usually asymptomatic). Moreover, even if domestic rubella virus is eliminated in future, it will be possible that the virus comes in from other countries. Therefore, to prevent CRS, high antibody prevalence and high antibody titers at the childbearing age must be maintained. For this purpose, seroepidemiological investigations by NESVPD monitoring the trend of the age-specific immune status should be kept on. The Preventive Vaccination Law amended in 1995 aims at immunizing all children. It seems necessary to examine the adequacy of an additional booster vaccination to maintain the immunity of pregnant women.