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Epidemiology of congenital rubella and results of rubella vaccination in Australia.

Congenital rubella was not notifiable in Australia until recently, but the national incidence of childhood deafness has been accurately documented since 1949. On the basis of these data and a study of congenital rubella in Western Australia, it is estimated that the national incidence of congenital rubella has decreased from a mean of at least 120 cases annually (one in 2,000 live births) to approximately 20 or less since 1977. This decrease has occurred since the introduction of rubella vaccination programs in 1971. The aim of these programs was to reduce the incidence of congenital infection by vaccinating girls (aged 10-14 years) at school without assessing their immunity. Nonpregnant seronegative women were also offered vaccination in family planning clinics as were postpartum seronegative women in obstetric units. By 1983, 96% of 8,226 pregnant women were seropositive for rubella antibody, as compared with only 82% of a similar group of women in 1971. This improvement in the immune status of pregnant women appears to be the result of rubella vaccination. Rubella vaccination also appears to have been successful in preventing congenital infection.

Adolescent↗

[Accumulative vaccination rate of rubella and positive antibody rate in an area of Japan--future problems with rubella].

The rubella vaccination rate remarkably decreased in Japan after a revised vaccination law was passed in 1994, as a result of which individual vaccination replaced mass vaccination at each school. We investigated the rubella antibody of 887 students and the accumulative rubella vaccination rate in an area of Okayama. The vaccination rate in Ibara, where children were inoculated individually, was 22.8%. In contrast, in Yoshii, where the vaccination was done as mass at each school, the rate was 89.8%. After 2003, when the transit period of the law ends, children 12-90 months of age will be the subjects for rubella vaccine. We presume that the vaccination rate in the future will reach 40-50% through accumulative vaccination. Such a rate of vaccination cannot prevent rubella epidemics and congenital rubella syndrome. In addition, an individual's rubella vaccination is generally done once during lifetime. We doubt whether the immune response induced by a vaccine can be maintained for more than 20 years without boosting. We think that a second vaccination is necessary for at least young girls, and this should be performed as mass at each school.

Adolescent↗

Description of a technique for the determination of the concentration and quality of rubella virus antibody molecules and experience with testing sera from humans with recent and past rubella infection.

The method of equilibrium filtration described by Fazekas and Webster (7, 8) for the determination of the concentration (A) and quality (K) of influenza virus antibody molecules was modified in order to permit such determinations to be made for rubella virus hemagglutination inhibiting (HI) antibodies. The technique was used for determining the A and K values of humans with recent and past rubella infection. Sera from patients collected within 59 days after onset of rubella rash were found to have larger K values than found for sera collected therafter or from persons with past rubella infection. The difference in K values was found not to depend on the levels of IgM rubella antibodies. Therefore, sera from persons with recent and past rubella infection can be distinguished by use of this technique independently from the relative concentrations of rubella IgM and IgG HI antibodies.

Antibodies, Viral↗

A recombinant rubella virus E1 glycoprotein as a rubella vaccine candidate.

A recombinant rubella virus E1 (rE1) glycoprotein was produced and some of its chemical and immunological features were characterized. Two animal models were then used to establish that the rE1 glycoprotein and rubella virus particles shared antigenic and immunogenic properties. In the first one, sera from rE1 glycoprotein-immunized BALB/c mice neutralized in vitro rubella virus infection. In the second model, severe combined immune deficient (SCID) mice implanted with tonsil fragments from rubella immune donors and immunized with rE1 glycoprotein produced human anti-rubella virus antibodies. Altogether, these results showed that immunization with rE1 glycoprotein elicited neutralizing anti-rubella virus antibodies. This study thus indicated that the rE1 glycoprotein could constitute a non-replicating rubella vaccine.

Animals↗

[Rubella in pregnancy: experimental studies on the value of gamma-globulin after rubella wild virus infection (author's transl)].

Rubella infection was produced with a wild rubella virus in 24 volunteers by intranasal application. Some of the subjects were given gamma-globulin intramuscular 24 hours later. In the control group clinically manifest rubella with massive viral excretion in the throat occurred in all in whom infection had taken place. In the majority of subjects rubella virus could be demonstrated in blood shortly before the skin rash appeared. High antibody titres occurred already 20 days after the infection. In subjects who were given gamma-globulin there were no clinical signs of rubella, viral excretion in the throat was diminished and shortened and viraemia was never demonstrated, antibody response was delayed and lower. But there was no significant decrease in the infection rate after gamma-globluin administration. It is concluded that early administration of a sufficient amount of rubella antibodies achieves inhibition of rubella virus multiplication and thus decreases significantly the risk of damage to the fetus.

Adult↗

Immunoglobulin G subclass antibodies to rubella virus in chronic liver disease, acute rubella and healthy controls.

Ten patients with chronic liver disease, seven healthy seropositive individuals with a remote history of rubella, and three patients with acute rubella were examined for serum levels of IgG subclasses and subclass antibodies against rubella virus structural proteins. One patient with AICAH had no detectable total or rubella specific IgG3 or IgG4. The liver disease patients were hypergammaglobulinemic and had greatly raised IgG1 levels. Patients with acute rubella lacked antibodies to the rubella virus E2 protein and showed no IgG4 antibody response. The liver disease patients showed a somewhat weaker IgG4 antibody response against the core (C) protein than healthy controls. However, differences are suggested within the subclasses in antibody reactivity against the individual rubella virus antigens. It is concluded that test systems that discriminate reactivities against individual antigens have to be used for characterization of viral antibody subclass profiles.

Acute Disease↗

Lymphocyte responses to rubella antigen and phytohemagglutinin after administration of the RA 27/3 strain of live attenuated rubella vaccine.

Lymphocyte phytohemagglutinin (PHA) responsiveness was found suppressed in both rubella sero-negative and sero-positive recipients of RA 27/3 strain of live attenuated rubella vaccine; the suppression was readily demonstrable only when a suboptimal dose of PHA was applied in the test. Lymphocytes from sero-negative vaccinees, which initially showed little or no in vitro response to concentrated rubella virus, became responsive after vaccination by day 21, when the highest sensitization to rubella antigen was seen. In the sero-positive vaccinees. lymphocytes responded to rubella antigen in vitro before vaccination, and in most cases vaccination did not result in significant changes in lymphocyte response. These results suggest that rubella vaccination leads to temporarily increased lymphocyte reactivity to rubella antigen, and the increased lymphocyte response to specific antigen may occur at the time of mild suppression of PHA response.

Adult↗

Immunosuppression and isolation of rubella virus from human lymphocytes after vaccination with two rubella vaccines.

Two groups of young rubella-susceptible women were vaccinated with two rubella vaccines. Heparinized blood samples were taken from all individuals the day of vaccination and 5, 7, 15, 21, 30, 35, and 42 days later. Purified lymphocytes from these samples were cocultivated with AGMK cells for rubella virus isolation. Parallel samples of lymphocytes were stimulated with phytohemagglutinin, and the rate of [14C]thymidine incorporation was determined. Rubella virus was isolated from lymphocytes collected on days 7, 15, and 21 after RA27/3 vaccination in contrast to days 7 to 35 after HPV77 vaccination. The lymphocyte response to phytohemagglutinin was markedly suppressed from day 5 to 15. Normal lymphocyte responses were restored within 1 month after vaccination with RA27/3, but even later (1 week) after HPV77 vaccine. Lymphocytes from rubella-susceptible persons infected invitro with rubella virus vaccines and stimulated with phytohemagglutin displayed a decrease in their responsiveness to the mitogen similar to that observed with lymphocytes from vaccinees. The transient immunosuppression observed in vaccinees is probably due to virus-induced functional damage of the lymphocytes since no direct cytocidal effect of rubella vaccine has been demonstrated on human lymphocytes.

Adult↗

Impaired cellular immunity to rubella virus in congenital rubella.

Specific cell-mediated immunity (CMI) responses to rubella virus were studied in 12 children with documented congenital rubella syndrome employing a (51)Cr lymphocytotoxicity microassay. Hemagglutination inhibition antibody was detected in 11 of the 12 children, with titers ranging from 1:4 to 1:128. CMI to rubella virus was demonstrated in only 3 of the 11 antibody-positive children. The 12th child was negative for both hemagglutination inhibition and CMI. Of the three children with a positive CMI response, two had histories of reinfection with rubella virus. These data suggest that congenital rubella infection produces an impaired CMI response which subsequently may be altered by reinfection with rubella virus. The lack of CMI in the presence of antibody and concurrent excretion of live virus in the child with documented congenital rubella infection suggest a factor to be explored in the pathogenesis of this disease.

Adolescent↗

Congenital rubella affecting an infant whose mother had rubella antibodies before conception.

A woman who had had high titres of rubella antibodies some months before she became pregnant gave birth to an infant in whom congenital rubella was confirmed at 4 months. Rubella haemagglutination inhibition tests, complement fixation tests, and immunofluorescence tests with anti-human IgG were carried out on sera from the mother. Rubella antibody titres in sera obtained in March 1971, seven and a half months before conception, were equivalent to 400 units, which is usually taken as indicating good immunity. Rubella virus was isolated from the baby's nose and throat in July 1973 but was not isolated from a cervical swab taken from the mother in December 1973; tests of her immunological competence did not show any definite abnormality. The presence of high levels of rubella haemagglutination inhibition antibodies does not invariably confer immunity or exclude the possibility of congenital rubella in a subsequent pregnancy.

Antibodies, Viral↗

New horizons in the control of rubella and prevention of congenital rubella syndrome in the Americas.

Data from the regional measles surveillance system have documented widespread rubella virus circulation in many different countries in the Americas. In response to the ongoing endemic incidence of the disease and the potential for a major rubella epidemics in the region, the Pan American Health Organization Technical Advisory Group on Vaccine Preventable Diseases recommended the implementation of a regional initiative to strengthen rubella and congenital rubella syndrome (CRS) preventive efforts in 1997. This article summarizes and highlights the progress toward accelerated rubella control and CRS prevention in the English-speaking Caribbean and in Chile, Costa Rica, and Brazil. Useful knowledge is being generated for the adaptation of similar rubella strategies elsewhere. The findings also document the feasibility of implementing the recommended strategies and their rapid impact on disease burden.

Adult↗

Rubella-specific IgG subclass concentrations in sera using an enzyme-linked immunosorbent assay (ELISA): the effect of different sources of rubella antigen.

Five rubella antigens were evaluated in an antiglobulin enzyme-linked immunosorbent assay for rubella-specific IgG subclass antibody. One monoclonal anti-human IgG subclass antibody was used for each of IgG1, IgG2 and IgG4, but two were compared for IgG3. A total of 101 sera were tested from cases of rubella in the distant past and from cases of primary rubella, reinfection and following immunization. Only one serum gave a discrepant result for specific IgG1, being positive with only one rubella antigen, a commercially prepared antigen coated on to microtitre wells (Enzygnost; Behringwerke). No sera contained detectable specific IgG2. Only four sera contained specific IgG4, and this was detectable only with Enzygnost antigen. For specific IgG3 little difference was observed between the two monoclonal anti-human IgG3 subclass antibodies; only two very weakly positive sera gave discrepant results. However, varying results were obtained for specific IgG3 with the different antigens. Enzygnost gave more positive results for specific IgG3 with most categories of sera. It is concluded that the differences between various reports of the rubella-specific IgG subclass profile cannot be explained entirely by the use of different rubella antigens.

Antibodies, Viral↗

Diagnosis of postnatal rubella by the enzyme-linked immunosorbent assay for rubella IgM and IgG antibodies.

A semi-automated enzyme-linked immunosorbent assay (ELISA) was established for the detection of rubella IgM antibodies in non-fractionated sera. A cut-off level between rubella IgM positive and negative sera was determined by a study of sera without rheumatoid factor from 200 blood donors. Testing of 12 donor sera containing rheumatoid factor showed that 5 sera gave a positive result in the rubella IgM assay. Rubella IgM antibodies were quantified by ELISA in a study of 214 serial serum specimens drawn from 16 patients with rubella during a period of up to 10 years after the infection. Peak values of the IgM antibodies were reached approximately 8 days after onset of the rash, and the persistence of the IgM antibodies ranged from 17-90 days, with the exception of one patient with a prolonged IgM response. The rubella IgG antibodies increased slowly after the rash and reached maximum levels about 50-120 days, after which a monor decrease was observed. The results of the present study indicate that ELISA is suitable as a routine procedure for the serodiagnosis of recent rubella.

Acute Disease↗

Rubella in Jerusalem. 1. Seroepidemiologic findings in children born after the 1972 rubella epidemic.

Nine hundred and sixty-nine babies born after a severe rubella epidemic were tested at the age of eight months for the presence of hemagglutination inhibition antibodies to the disease. There were 208 (21.9%) seropositive babies with titers of greater than or equal to 1:16. Seven cases of congenital rubella were diagnosed at birth, 14 were confirmed by eight months and two babies, who were considered normal at the age of eight months, developed late signs of the disease. Less than 3% of the mothers of the seropositive babies had had clinically recognized rubella in pregnancy. If positive hemagglutination inhibition antibody to rubella accurately reflects congenitally acquired rubella infection, between 8.1 and 21.9% of the 969 babies had serologic evidence of the disease. For cases of congenital rubella diagnosed by the age of three years, the limits are between 8.9 and 23.7 per 1,000 live births for the risk of the disease at the height of the epidemic. Rubella vaccine was not available in Israel until after the 1972 epidemic, the effects of which justify the continued search for and immunization of seronegative women of childbearing age, in addition to routine immunization of young girls.

Adult↗

Control of rubella and congenital rubella syndrome (CRS) in developing countries, Part 1: Burden of disease from CRS.

Congenital rubella syndrome (CRS) can lead to deafness, heart disease, and cataracts, and a variety of other permanent manifestations. In developing countries, the burden of CRS has been assessed as follows: by surveillance of CRS; by surveillance of acquired rubella; by age-stratified serosurveys; and by serosurveys documenting the rubella susceptibility of women of childbearing age. During rubella outbreaks, rates of CRS per 1000 live births were at least 1.7 in Israel, 1.7 in Jamaica, 0.7 in Oman, 2.2 in Panama, 1.5 in Singapore, 0.9 in Sri Lanka, and 0.6 in Trinidad and Tobago. These rates are similar to those reported from industrialized countries during the pre-vaccine era. Special studies of CRS have been reported from all WHO regions. Rubella surveillance data show that epidemics occur every 4-7 years, similar to the situation in Europe during the pre-vaccination era. In developing countries, the estimated average age at infection varies from 2-3 years to 8 years. For 45 developing countries we identified serosurveys of women of childbearing age that had enrolled > or = 100 individuals. The proportion of women who remained susceptible to rubella (e.g. seronegative) was < 10% in 13 countries. 10-24% in 20 countries, and > or = 25% in 12 countries. Discussed are methods to improve the surveillance of rubella and CRS in developing countries.

Adolescent↗

Accelerated rubella control and congenital rubella syndrome prevention strengthen measles eradication: the Costa Rican experience.

In 2000, Costa Rica set a goal for accelerated rubella control and congenital rubella syndrome (CRS) prevention in conjunction with its established measles eradication goal. To achieve this goal, a National Plan of Action for the integration of a measles-rubella (MR) vaccination strategy was implemented. The components of the national plan included conducting a national vaccination campaign with a single dose of MR vaccine for men and women aged 15-39 years, establishing routine postpartum MR vaccination of all previously unvaccinated women, maintaining high coverage among children with two doses of measles-mumps-rubella vaccine, strengthening the integrated measles and rubella surveillance system, and developing a CRS surveillance system. This report summarizes the results of a successful adult campaign. Targeting MR vaccination appropriately and using the opportunity to strengthen surveillance for rash illness has benefits beyond accelerated rubella control and CRS prevention, including strengthening of the measles eradication program.

Adolescent↗

Comparison of a whole-virus enzyme immunoassay (EIA) with a peptide-based EIA for detecting rubella virus immunoglobulin G antibodies following rubella vaccination.

A total of 250 human serum samples were tested for rubella virus immunoglobulin G antibodies by two enzyme immunoassays (EIAs), one using whole rubella virus antigen and the other based on the use of synthetic peptide antigen. The samples were taken from 125 volunteers before and after their immunization with the RA 27/3 rubella vaccine. This study indicates that a synthetic peptide-based EIA can favorably replace current viral lysate-based EIAs to detect rubella virus antibodies following immunization. Because the synthetic peptide used in this newly developed EIA represents a putative neutralization epitope of the rubella virus, it could also be instrumental in determining rubella immune status and in assessing vaccine program efficiency.

Adult↗

Rubella and congenital rubella syndrome in Japan: epidemiological problems.

Rubella virus infection can lead to problems with congenital rubella syndrome (CRS) in the next generation due to fetal infection, but these problems are preventable with vaccination. In other words, rubella epidemics and the occurrence of CRS can be eliminated by vaccination. In Japan, until recently, rubella epidemics occurred every 5 years, and there were at least 1,600 CRS cases between 1965 and 1985. Following the 1994 revision of the Preventive Vaccination Law, national surveillance from approximately 3,000 clinics has shown that the number of rubella cases has dramatically decreased to a few thousand and the occurrence of CRS has decreased to only a few cases. However, the vaccination rate during a transitional period from 1995 to 2003 has been unsatisfactory. This has been especially true for junior high school students, because individual vaccination has replaced mass immunization in urban areas. As a result, the negative antibody rate in females below 18 years of age has increased to approximately 27%. If this trend continues, there is likely to be an increase in rubella epidemics and occurrence of CRS in the near future. Vaccination is not compulsory under Japanese law, and vaccination campaigns alone have proved unsuccessful in promoting vaccination. Another system of motivating individuals to seek vaccination will be needed in order to maintain a high vaccination rate without such campaigns.

Antibodies, Viral↗