The Topic of This Month Vol. 32, No. 9 (No. 379)

Rubella and Congenital Rubella Syndrome in Japan, as of August 2011
(IASR 32: 250-252, September 2011)

Rubella is caused by rubella virus, a member of the genus Rubivirus in the family of Togaviridae .  The principal symptoms are fever, rash and cervical lymphadenopathy.  Some cases show only a part of these symptoms and some others show measles-like or erythema infectiosum-like symptoms (see p. 257 & 258 of this issue and IASR 32: 170-171, 2011).  The definitive diagnosis requires laboratory data (  It is generally a mild disease with good prognosis.  Rare complications include thrombocytopenic purpura and encephalitis.  Transient arthritis has been observed in some adult cases.  The virus when infecting a pregnant woman during an early stage of pregnancy occasionally causes congenital rubella syndrome (CRS) in newborns, such as cataract, congenital heart failure, or dysacousis (IASR 24: 59-60, 2003 & 27: 94-96, 2006), or less frequently intrauterine death (p. 259 of this issue).

Japan experienced local outbreaks in 2011 after seven yearsf absence.  To cope with rubella infection including CRS, to which no specific therapy is available, vaccination is only effective measures that can be taken.

The National Epidemiological Surveillance of Infectious Diseases (NESID): Rubella is a Category V infectious disease under the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections.  It had been monitored through sentinel surveillance until 2007, but since 2008 on, all the cases are required to be notified (IASR 29: 53-54, 2008).  While having declined gradually from 2008 to 2010 (294, 147 and 90 in respective years), reported cases increased to 272 cases already in the week 30 of 2011 (Fig. 1).  In total 803 cases reported since 2008, 492 accompanied laboratory diagnosis. The large number of rubella cases in 2008 may have been contaminated by measles cases, because the year 2008 experienced measles outbreak and 54% of reported rubella cases in this year were based on clinical observation only.

Case distribution among prefectures is shown in Fig. 2.  In 2011, Kanagawa, Fukuoka and Osaka respectively reported 55, 45, and 41, totaling about half of the cases.  More than a few cases were reported from outbreaks among male adults in workplaces (see p. 252 & 254 of this issue).  While 0-4 year children were the most frequent among all the age groups in 2008, in 2011 adults (most frequently in their 20's-40's) occupied 81% of the cases (Fig. 3).  In 2011, the incidence was higher in males than in females (the sex ratio was 3.1 for all cases and 4.2 for the age group of 20-49 years).

Since April 1999 and since 5 November of 2003, respectively, CRS and acute encephalitis (rubella encephalitis included) have been Category V infectious diseases requiring notification of all the cases.  Until August 2011 since the start of the surveillance, 19 CRS cases (Table 1 in page 252) and one rubella encephalitis case (a man in his 40's) have been reported.  Among the mothers of these CRS cases, none except one had a clear history of vaccination.  Mothers of 13 cases experienced symptomatic rubella during pregnancy and those of four cases did not.  It is interesting to note that, among five CRS cases reported since 2005, three cases were from mothers infected abroad.

Rubella virus: Rubella virus has 13 genotypes, which can be grouped into two clades.  Since 1960 till 2004 at least, genotypes 1a, 1D and 1j were the majority in Japan (there have been few isolations since 2005 till recently).  The isolates in 2011 in Japan are predominantly genotypes 1E and 2B (see p. 252-259 of this issue).  Noting that the currently predominant genotypes in the world are 1E, 1G and 2B (see p. 260 of this issue), rubella viruses circulating in Japan now are probably derived from the imported ones that subsequently expanded in Japan.  The genotypes of the current isolates are different from the genotype of the vaccine strain (1a).  However, as all these genotypes share a common serotype, the currently used vaccine is considered effective to all the epidemic strains.

Immunization with rubella vaccine: To prevent CRS, the routine immunization to the female junior high school students with rubella vaccine started in 1977.  Since 1995, it was expanded to the both sexes for prevention of rubella epidemic and given as routine immunizations to children at 12-90 months of age and to those in the junior high school.  Since 2006, immunization with measles-rubella combined vaccine (MR vaccine) has been conducted with the two-round schedule, i.e., at one year of age as the first round (the 1st vaccination) and one year preceding the primary school entry (5-6 years of age) as the second round (the 2nd vaccination) (IASR 27: 85-86, 2006).  In 2008, as a five-year program, the second round immunization was expanded for age group of the first grade of the junior high school, 12-13 years of age (the 3rd vaccination) and age group of the third grade student of the high school, 17-18 years of age (the 4th vaccination) (IASR 29: 189-190, 2008).  Coverage of MR vaccine was 96% for the 1st, 92% for the 2nd, 87% for the 3rd and 79% for the 4th vaccination.  The rates of the 1st and 2nd vaccinations were sufficiently high, but those of the 3rd and the 4th vaccinations need further improvement (see p. 262 of this issue).

*Note: The schedule does not intend to give four doses.  With the age distance between the target groups and on account of the limited time span of the temporal measures, any person under age of 18 has a chance of receiving two shots but not more.  Missing the chance of immunization during the target age, he/she misses the chance of vaccination under this regime entirely (though they are free to receive vaccination with their own expense).

National Epidemiological Surveillance of Vaccine Preventable Diseases (see p. 263 of this issue): Prefectural public health institutes in Japan jointly survey every year rubella hemagglutination inhibition (HI) antibody level.  About 5,000 healthy people have been participating.  According to the data of 2010 (Fig. 4), women in their 30's to 40's showed high HI antibody prevalence (90-95%) presumably reflecting the rubella routine immunization to the female junior high school students during 1977-1994, while men of the same age group had significantly lower seroprevalence (70-80%).  The rubella epidemic in 2011 occurred mainly in this male age group.  As for children, while HI antibody positive rate was 30-40% before the introduction of MR vaccine, in 2010 the rate among one-year babies attained 66% and that of two-year infants 95% owing to the MR vaccine introduced in 2006.  Fig. 4 also shows that high proportion of the target age groups of the 2nd, 3rd and 4th vaccinations have received immunization twice, indicating the success of the new vaccination schedule implemented in 2006 and 2008.

Measures to be taken in future: In 2004, a research group commissioned by Ministry of Health Labour and Welfare announced an emergency proposal ( warning the risk of CRS of babies born to women with low rubella antibody, and it created, so as to avoid unnecessary artificial abortion, CRS consultation sites (see p. 266 of this issue) for clinicians concerning the detection and evaluation of cases at risk and consultation of pregnant women.

Western Pacific Regional Office of WHO targets 2015 for the regional reduction of rubella cases to less than 10 per million population and CRS to less than 10 per million births.  Many countries have introduced MR vaccine (see p. 267 of this issue).  For eliminating rubella and CRS, high quality surveillance assisted by laboratory confirmation of all cases is desirable.

To increase the vaccination coverage, which is crucial for the rubella control, education of junior high and high school students on the importance of measles and rubella control and prevention of CRS is necessary, for which commitment of Ministry of Education, Culture, Sports, Science and Technology is indispensable.  Pregnant women are at risk of rubella infection transmitted by her husband or other family members (J Obstet Gynaecol Res 32: 461-467, 2006).  Vaccination to the women expecting pregnancy or to family members of pregnant women on request is desirable.  In order to prevent outbreaks in workplaces, vaccination to the adults in possible consultation with the industry doctors should be considered.

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