If a pregnant woman acquires infection during an early stage of pregnancy, the virus will occasionally be transmitted to the fetus through placenta, causing congenital rubella syndrome (CRS) in the newborn. Timing of the fetal infection determines the extent of teratogenic effects; the most common permanent defects are neurosensory deafness, cataract/glaucoma, and heart disease. To prevent CRS, individual protection must rely upon immunizing uninfected women against rubella by vaccination, and mass protection upon control of rubella epidemic itself by increasing the vaccine coverage among children and avoiding exposure of pregnant women to rubella virus.
History of rubella vaccination in Japan: Voluntary immunization with rubella vaccine began in 1976. Routine immunization of female students of junior high schools began in August 1977 under the Preventive Vaccination Law (see p. 55 of this issue). After April 1989, measles-mumps-rubella (MMR) vaccine has been permitted to choose instead of regular measles vaccination of children of 12 months to 72 months old. Although the inoculation of MMR vaccine was stopped in April 1993 due to the occurrence of many aseptic meningitis cases (see IASR, Vol. 15, No.9), inoculation with rubella vaccine of children of both sexes at the age of 12 months to 90 months began in April 1995. Junior high school students of both sexes were subjected to routine immunization for a term until September 30, 2003. Because the rate of vaccination of the latter is very low, nonvaccinees of both sexes born during April 2, 1979 and October 1, 1987, are required to receive routine immunization as a temporary measure until September 30, 2003, in compliance with the partial amendment of the Preventive Vaccination Law in November 2001.
Rubella vaccine coverage: The rubella vaccine coverage of children of 12 months to 90 months of age as routine immunization was as high as 97% in 2001, while that of junior high school students was as low as 39% according to the Ministry of Health, Labour and Welfare. The vaccine coverage of junior high school students is on the yearly decrease and that of 2001 was the lowest after the amendment of the Preventive Vaccination Law in 1994 (see p. 55 of this issue).
Rubella cases and CRS cases: According to the reports from pediatric sentinels under the National Epidemiological Surveillance of Infectious Diseases, nationwide epidemics of rubella have occurred approximately every 5 years; in 1982, 1987-88, and 1992-93 (see IASR, Vol. 21, No.1). No further nationwide epidemics have occurred since 1994; cases have markedly decreased to as few as 2,561-4,366 (0.85-1.62 per sentinel) after 1999 (Fig. 1). As the age distribution of cases shows in Fig. 2, cases are distributed evenly between 0 and 9 years of age with a slight increase seen in one-year old children; infants aged under 4 years account for about 50% of all cases.
CRS is one of the category IV notifiable diseases under the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (the Infectious Diseases Control Law) and all physicians who have diagnosed it must report to the nearby health center within 7 days. The number of CRS cases reported after enactment of the Infectious Diseases Control Law in April 1999 as of February 18, 2003, is three; one in June 2000 (the 26th week) in Osaka Prefecture, another in July 2001 (the 29th week) in Miyazaki Prefecture, and the other in December 2002 (the 51st week) in Okayama Prefecture (see p. 59 of this issue).
The incidence of rubella by prefecture is shown in Fig. 3. Although no nationwide epidemics are seen, small-scale local epidemics occur every year. It is noteworthy that a relatively large number of rubella cases were reported in 2000 in Miyazaki Prefecture, where a CRS case occurred in 2001. There was an outbreak of rubella in 2002 at a primary school in Okayama Prefecture (see p. 58 of this issue), where a CRS case was reported in the same year.
Antibody prevalence: According to the National Epidemiological Surveillance of Vaccine-Preventable Diseases conducted during July-September 2001 (Fig. 4), the prevalence of rubella HI antibody among females at ages over 18 years was as high as 94%, whereas that among males was low, being 79%. CRS occurs mostly from primary infection during pregnancy; among pregnant women with low antibody titer may sometimes develop the disease even upon reinfection (see p. 59 of this issue). Although the exact titer just before reinfection has not been clarified, attention must be paid to the fact that reinfection occurred in a woman with an HI antibody titer of 64 (see IASR, Vol. 21, No. 1). Those girls of 11 years old subjected to the survey performed in 1997 showing a low antibody-positive rate (see IASR, Vol. 21, No. 1) became 15 years old at the 2001 survey. The antibody-positive rate among these girls was markedly low compared with other ages, being 54%. Among younger generations, no difference in the antibody-positive rate can be seen any longer between males and females (see p. 57 of this issue). From this survey, the population of women susceptible to rubella younger than 40 years was estimated at more than 3,500,000, of which susceptible population of 20s and 30s were estimated at more than 700,000. The susceptible male population of 20s and 30s was larger than female population, being over 4,500,000 (see p. 55 of this issue).
Comparison between vaccine strains and recently isolated wild strains: The parental strains of the rubella vaccine now produced and used in Japan are those isolated during 1966-1969. From the analysis of all nucleotide sequences encoding membrane protein E1 of rubella virus, little difference was seen in the genome structure of the antigen epitope sites, participating in neutralization and hemagglutination, between the vaccine strains and the wild strains prevailing now (see p. 61 of this issue).
Promotion of rubella vaccination: Routine immunization with rubella vaccine has been applied to not only junior high school students but also to children of 12 months to 90 months of age from April 1995 by the 1994 amendment of the Preventive Vaccination Law. Owing to this program, nationwide rubella epidemics have been suppressed, nevertheless if the rate of vaccination is insufficient, susceptible individuals will accumulate and large-scale nationwide rubella epidemics in near future are anticipated in Japan like that occurred in Greece in 1999 (BMJ, 319:1462-1467, 1999). Women at the age of 15 years with low antibody prevalence at the time of survey in 2001 will be 17 years in 2003. The rubella vaccination program for all males and females born between April 2, 1979 and October 1, 1987, is being done routinely in compliance with the Preventive Vaccination Law, nevertheless the program is not well known and the rate of vaccination among those cohorts is still low. Since CRS cases are born even in small-scale local epidemics, active measures by each local government (see p. 62 of this issue) are necessary so that more subjects can be vaccinated against rubella within 6 months before September 30 of this year. Besides, it is desirable that rubella-unaffected and rubella-unvaccinated females other than recipients of routine immunization receive voluntary immunization more than 2 months prior to pregnancy.