Epidemiological characteristics of rubella and congenital rubella syndrome in the 2012-2013 epidemics in Tokyo, Japan.

A large rubella outbreak has been observed since June 2012 in Tokyo, Japan, and a rapid increase in the number of congenital rubella syndrome (CRS) cases have also been reported in Japan since October 2012. All the clinically diagnosed and laboratory-confirmed rubella cases reported in Tokyo from January 2012 to December 2013 and all the laboratory-confirmed CRS cases from January 2012 to March 2014 were analyzed. In total, 4,116 rubella cases were reported in Tokyo. Of these, 77.2% (n=3,176) were male; the highest number of cases occurred in males aged 35-39 years and in females aged 20-24 years. Complications included arthralgia/arthritis (19.4%), thrombocytopenic purpura (0.5%), hepatic dysfunction (0.3%), and encephalitis (0.1%). The circulating rubella virus in Tokyo was genotype 2B. The most possible site of transmission was the workplace. Because of the rubella epidemic, 16 CRS cases were reported in Tokyo from March 2013 to February 2014. Domestic infection with rubella was proven for all mothers of 16 cases. This situation suggests that Japan is still working to achieve rubella elimination.

Surveillance of congenital rubella syndrome in Japan, 1978-2002: effect of revision of the immunization law.

Infection of rubella virus at the early stages of pregnancy in women who are not immune to rubella often induces congenital anomalies in infants, namely congenital rubella syndrome (CRS). This paper is the first comprehensive report of CRS cases in Japan, compiled from a questionnaire to major hospitals, reports to journals and academic meetings, and cases for virus/virus genome verification submitted to the National Institute of Infectious Diseases. CRS incidence in Japan was determined to be 0.2-8.1 cases/100,000 live births per year in epidemic years and 0.1-0.7 in non-epidemic years, respectively. In the last 4 years, the number of CRS cases remarkably decreased to one-three cases per year. This decrease is thought to be because the immunization law was revised in 1994 for changing the focus of rubella immunization from junior high school girls to infants of both sexes.

Molecular epidemiology of rubella virus in Asia: utility for reduction in the burden of diseases due to congenital rubella syndrome.

BACKGROUND: Rubella is a mild disease mainly of infants, involving a rash and a fever. However, when women who have no immunity to rubella are infected during the early stage of pregnancy, their babies are often born with congenital rubella syndrome (CRS), which is characterized by a few disorders including deafness, cataracts and heart malformations. To prevent CRS, several strains of live attenuated rubella vaccine have been developed and introduced into immunization programs in many countries. In most Asian countries except Japan, Singapore and Taiwan, rubella remains uncontrolled, and the burden of diseases from CRS is high. In order to develop a control program to reduce the number of CRS cases in Asian countries, it is necessary to conduct a survey of rubella and CRS cases, and to then determine the genotype of the circulating rubella virus in each country. METHODS: Cases of rubella and CRS, based on national reporting systems or active surveillance in the Asian countries, are summarized. Sequences of the E1 gene of the virus isolates from the Asian countries were compared by phylogenic analysis. RESULTS: Recent studies of the molecular epidemiology of rubella virus worldwide revealed that there are two genotypes, and that genotype I is circulating almost worldwide, while genotype II is an Asian prototype restricted to the Asian continent. Genotype I viruses fall into a number of groups, some of which are geographically localized. Antigenically these two genotypes are cross-reactive and immunization with either virus results in immunity to all rubella viruses. DISCUSSION: The hypotheses that rubella virus has evolved on the Asian continent is proposed. The World Health Organization (WHO) has recognized that a rubella immunization program can be combined with the measles immunization program. Inclusion of rubella in the expanded program of immunization (EPI) of measles would be ideal in Asian countries, as it would be efficient and cost effective to administer one injection containing a three-combined vaccine (MMR). It would also be desirable given that WHO require laboratory tests to confirm the presence of measles or rubella as part of it's measles control project, because rubella is often misdiagnosed as measles.

Congenital rubella syndrome due to infection after maternal antibody conversion with vaccine.

We experienced a case of congenital rubella syndrome (CRS) due to infection after maternal antibody conversion with vaccine. The mother was immunized with rubella vaccine at 14 years of age, and was confirmed as having rubella-specific hemagglutination inhibition (HI) antibody at the 1:16 level both at ages 26 and 30 during preceding pregnancies. At the second week of the third gestation, her second child developed rubella. She did not suffer any symptoms, but was found to have rubella HI antibody at the 1:512 level at 9 weeks of gestation. She delivered a male baby weighing 2,545 g at 38 weeks of gestation. He had congenital pneumonia, patent ductus arteriosus, bilateral cataracts, sensorineural deafness, and periventricular calcification of the brain. The rubella-specific antibody was 1:512 by HI and 10.1 by IgM enzyme-linked immunosorbent assay. According to these observations, he was diagnosed as having CRS. The rubella virus genome was detected in the fluids of the vitreous body using RT-nested PCR. This case emphasizes the importance of double-dose immunization (once in infants and once in young adults) in order to obtain an adequate level of antibody with duration sufficient to ensure the prevention of CRS.

[The present situation and limitation of antibody assays for diagnosis of rubella virus infection in pregnant women].

Rubella virus infection during early stages of pregnancy often results in a number of developmental disorders referred to as congenital rubella syndrome(CRS). Both clinical and laboratory diagnosis of suspect cases of CRS can be made with relative ease, particularly when expectant mothers show the typical rubella-specific rash. Serological diagnosis of CRS is accomplished using hemagglutination inhibition (HI) and enzyme-linked immunosorbent(IgM-EIA) assays. Antibody titers as determined by these assays are generally very high following acute apparent rubella infections, thus making serological diagnosis relatively easy in most cases. However, the detection of possible CRS cases can be hampered by clinically inapparent rubella infections during early pregnancy. As much as 30 percent of all acute rubella cases are inapparent infections, and there is the very real potential for such inapparent infections to occur during pregnancy, to result in fetal infections, and consequently to cause CRS. Detection of CRS becomes extremely difficult in such settings. Complicating CRS detection even more are rare rubella re-infections that might occur in early pregnancy, and unknown risk of fetal infection and CRS. In re-infection cases, HI antibody titer becomes elevated due to a secondary immune response, and IgM antibody is produced in a significant number of cases. To determine directly the fetal infection, virus genome detection was developed and applied clinically for the past decade. Using a combination of serological and genomic detection methods, the results of the investigation suggest that when rubella infection during early pregnancy occurs 1) there is a significant risk of fetal infection that results from acute apparent rubella infection, 2) there is a measurable risk of fetal infection resulting from inapparent infections as defined by HI antibody titers > or = 256 and with and IgM-EIA index > or = 7, and 3) high HI antibody titers with low IgM-EIA indices or no detectable IgM antibody in cases of inapparent rubella infections may represent rubella re-infections and result in a low risk of fetal infections.

Global distribution of rubella virus genotypes.

Phylogenetic analysis of a collection of 103 E1 gene sequences from rubella viruses isolated from 17 countries from 1961 to 2000 confirmed the existence of at least two genotypes. Rubella genotype I (RGI) isolates, predominant in Europe, Japan, and the Western Hemisphere, segregated into discrete subgenotypes; international subgenotypes present in the 1960s and 1970s were replaced by geographically restricted subgenotypes after approximately 1980. Recently, active subgenotypes include one in the United States and Latin America, one in China, and a third that apparently originated in Asia and spread to Europe and North America, starting in 1997, indicating the recent emergence of an international subgenotype. A virus that potentially arose as a recombinant between two RGI subgenotypes was discovered. Rubella genotype II (RGII) showed greater genetic diversity than did RGI and may actually consist of multiple genotypes. RGII viruses were limited to Asia and Europe; RGI viruses were also present in most of the countries where RGII viruses were isolated.