Studies on Rubella in Pregnancy: Report of the Public Health Laboratory Service Working Party on Rubella

In a further survey of women of child-bearing age neutralizing antibody to rubella virus was found in 80 to 96% of those sampled from different parts of the country.When assessment was restricted to susceptible pregnant contacts and rubella in the index case was confirmed by virus isolation immunoglobulin in the dosage used did not appear to give any appreciable protection.One instance of a confirmed second attack after known exposure to rubella among more than 100 immune contacts is recorded.The implications of all these findings are discussed.     

Congenital Perceptive Deafness: Role of Intrauterine Rubella

Rubella antibody was detected in 85 (61%) of 139 children aged from 6 months to 7 years with congenital perceptive deafness. Of the 112 children who were aged under 4 years 61 (54%) had rubella antibody (seropositive) compared with 7·1% in randomly selected children of the same age. A close correlation was found between the presence of antibody in children with perceptive deafness and (1) a maternal history of rash or contact in early pregnancy, and (2) with the presence of other rubella-type defects. Intrauterine rubella was thought to be the cause of the deafness in 82 (59%) of the 139 children, in 60 of whom deafness was the only rubella defect detected. Thus intrauterine rubella should be considered a likely cause of congenital perceptive deafness in a child under 4 years in whom rubella antibody is present.     

The Need for Routine Rubella Antibody Testing of Women

Results of rubella antibody tests performed by the California State Viral and Rickettsial Disease Laboratory on blood specimens collected in 1968 and 1969 from school children and women of childbearing age showed a slightly lower prevalence of rubella antibody in California than reported from most other areas of the United States. Among women of childbearing age, rubella hemagglutination-inhibition (hi) antibody was found in 72 percent of those tested in California compared with 80 percent to 90 percent in other areas of the country.Rubella antibody testing services offered by the State Virus Laboratory included situations in which a pregnant woman was exposed to a suspected case of rubella. It was shown that very few of these exposures constitute a significant risk to the fetus as most of the women already possessed antibody to rubella from past infection and in many instances the exposures were not to actual cases of rubella.The results of this study emphasized the urgency of obtaining blood specimens from pregnant women as soon as possible after exposure to rubella or development of symptoms of rubella. The urgency and anxiety attending these situations can largely be obviated if routine rubella antibody testing of women is carried out prior to pregnancy or at the first prenatal visit.     

Rubella: immunity and vaccination in schoolgirls.

Of 191 schoolgirls, 128 volunteered to take part in a feasibility study of serotesting before and after rubella vaccination, and all responded to RA 27/3 vaccine. Had the serum samples been taken by a fingerprick method the number of volunteers would probably have increased considerably. A change in policy for rubella vaccination to testing both before and after vaccination would cost no more than the existing policy, would ensure primary response, and would differentiate those women who were protected by the vaccine from those with antibody to wild virus.     

Rubella screening and immunisation of schoolgirls: results six to seven years after vaccination.

A long term follow-up study was carried out of girls given RA27/3 or Cendehill rubella vaccine in their 13th-14th year compared with a group of girls who had been found to be naturally immune at the age. A high proportion of the girls in all groups had persistent rubella antibody six to seven years after inclusion in the study, although some of these would have been considered to be susceptible to rubella by methods currently in use for screening for rubella antibody. Great care should be taken in interpreting the efficiency of the schoolgirl immunisation policy in the United Kingdom; women in their childbearing years who may have received vaccine but are found by a screening test to be seronegative should be retested by a more sensitive procedure before a final report is made.     

Seven-Year Follow-Up Study of Rubella Syndrome in Ryukyu with Special Reference to Persistence of Rubella Hemagglutination Inhibition Antibodies

Rubella hemagglutination inhibition (HI) antibodies in 266 children with rubella syndrome born in 1965 in the Ryukyu Islands and their mothers were followed for seven years. Titers of rubella HI antibody in the mothers declined slowly, while those in the children declined rapidly up to 40 months of age. Thereafter decline of titers became extremely slow and only seven cases (three per cent) became seronegative for rubella HI antibody. Rubella HI antibody titers seemed to have no particular correlation to the severity of clinical manifestations.     

Clinical and Serological Assessment of Children Exposed in Utero to Confirmed Maternal Rubella

As a result of the work of the Public Health Laboratory Service Working Party on Rubella (1970) it was possible to examine the children of 60 susceptible women who were in contact with rubella during their pregnancy and who subsequently showed serological evidence of the infection, despite immunoglobulin prophylaxis. When the children were assessed between 8 months and 4 years 8 months of age a blood sample was also taken and tested for rubella antibodies so that a retrospective diagnosis of congenital rubella infection could be made. Only 19% of children exposed to subclinical maternal rubella showed evidence of intrauterine infection compared with 53% of those born to mothers who had clinical rubella. One of the 26 children exposed to subclinical maternal infection had a rubella defect, compared with 9 of the 34 children exposed to clinical maternal rubella.     

Comparison of Fluorescent Antibody Induced by Rubella Virus in Vaccinee and Convalescent Individuals

Specific rubella antibody detectable by indirect immunofluorescence developed in response to immunization with attenuated rubella vaccine, HPV-77, DK-12. Fluorescent antibody (FA) was found when vaccinee sera were reacted with antigens synthesized in three different acutely infected continuous cell lines: BHK-21, LLCMK-2, and RK-13. FA titers were high, and they correlated with antibody titers obtained by hemagglutination-inhibition tests. Levels of FA in vaccinated individuals were slightly lower than those found in persons recovered from natural rubella infections. Rubella FA persists a long time in convalescent individuals and appears to be maintained for at least 19 months in vaccinees.     

Rubella antibody titres and immunization status in a family practice.

Rubella vaccination status and immunity to rubella were studied in 230 "active patients" aged 8 to 22 years in a teaching family practice by means of a chart review and measurement of the rubella antibody titre in a blood sample. Of the 200 patients who submitted a blood sample 161 (80%) were found to be immune, having a rubella hemagglutination-inhibiting antibody titre of 1:16 or greater. Log linear analysis showed that immunity to rubella was independent of a history of rubella, and that 94% of the vaccinated patients versus 74% of the unvaccinated patients (a significant difference; P = 0.007) were immune. In retrospect we estimated that 80% of the study group were protected at the start of the study. After surveillance and follow-up, with vaccination of 27 of the 39 patients identified as susceptible to rubella, this estimated proportion increased to 90%. The study showed that there is nothing to be gained by asking about a history of rubella but that vaccination against this disease is increasing among children aged 5 to 9 years.     

Modified Hemagglutination-Inhibition Test for Rubella Employing Human Group O Erythrocytes

A hemagglutination-inhibition (HI) test for rubella is described which utilizes human group O, rather than 1-day-old chick, erythrocytes. The test was found to be as sensitive and reproducible for detection of rubella antibody as HI tests employing chick erythrocytes. Advantages to the use of human erythrocytes are (i) they are more available, (ii) it is unnecessary to absorb natural agglutinins from human test sera, and (iii) heparin-MnCl₂-treated sera do not agglutinate human erythrocytes, as is sometimes the case with chick erythrocytes. Factors influencing the reliability of the test are discussed.     

Rubella in Russia: variability of the infectious agent during the period of vaccine prophylaxis

AIM: To assess influence of vaccination against rubella on the genetic diversity of rubella virus. MATERIALS AND METHODS: Vaccine strains of rubella virus Wistar 27/3 and Orlov-B as well as sera from patients with rubella obtained in Perm region during 1999 - 2005 period and standard serologic, molecular, epidemiologic and statistical methods were used. The study was performed according to the WHO recommendations on the genotyping of wild rubellavirus strains. RESULTS: Strains of rubella virus isolated in Perm region, vaccine strain Orlov-B (Saint Petersburg), and 4 Russian strains isolated in 1967-1997 before vaccine introduction belong to the same genetic group with high degree of homology - genetic divergence do not exceed 0 - 1%. This group was identified as genotype 2c which, according to WHO's data, circulates only in Russia. Periods of epidemic peaks of rubella incidence and its falls as well as selective immunization of girls and women of childbearing age did not influence on the genetic stability of the virus (divergence did not exceed 0.6 - 2.0%). On the contrary, mass immunization of children aged 1 - 2 years during 4 years resulted in statistically significant changes of rubella virus subtype inside the genotype 2c. CONCLUSION: Ten-year experience of rubella vaccination in Perm region demonstrates necessity of inclusion of monitoring for rubella virus variability in the system of epidemiological surveillance and control for rubella infection during period of its prevention by vaccine.     

The preparation of bacterial luciferase conjugates for immunoassay and application to rubella antibody detection

Bacterial luciferase has been modified with the thiolating reagent S-acetylmercaptosuccinic anhydride and covalently crosslinked to either Staphylococcus aureus protein A or anti-human immunoglobulin G (IgG) with the heterobifunctional reagent m-maleimidobenzoic acid N-hydroxysuccinimide ester. The conjugates retain enzymatic light-emitting activity and have the ability to bind IgG antibody. The ability of these conjugates to detect human IgG has been demonstrated by application to rubella immunity screening. Rubella antibodies are isolated from serum on the surface of rubella antigen-coated tubes and subsequently determined by light emitted from bound conjugate. In a preliminary study, the bioluminescent immunoassay has been compared to a commercial rubella antibody radioimmunoassay and found to be comparable in the ability to determine rubella immunity.     

Loss of Rubella Antibody from Immune Globulin Treated with Kaolin

Sera and immune globulin (IG) preparations are customarily treated with kaolin before titration of their rubella hemagglutination-inhibiting (HI) antibody in order to rid them of nonspecific inhibitors of hemagglutination. The treatment was shown in this investigation to have no adverse effect on the antibody level of the sera but was found to remove considerable amounts of gamma-globulin from IG preparations. Evidence of this removal was obtained by serological tests, by spectrophotometric determination of protein concentration and by disc electrophoresis. In contrast to kaolin, heparin-manganese chloride (MnCl(2)) treatment of IG preparations had essentially no effect on the level of antibody globulin by all the criteria used. Heparin-MnCl(2)-treated IG lots were in these respects similar, if not identical, to their untreated counterparts. Since nonspecific inhibitors associated with the beta-lipoprotein fraction of serum are removed by the method employed to fractionate the IG samples, it seems unnecessary to treat the latter in any way for the HI test. No difficulty was encountered in this investigation with several untreated IG lots.     

Immunoglobulin Responses in Rubella and its Complications

Normal responses of rubella-specific IgG and IgM antibody were assessed in eight patient by immunofluorescence. A prolonged rubella-specific IgM response was shown in three patients with complications of rubella infection. Two patients had thrombocytopenic purpura and one had carpal-tunnel compression.     

Study of interaction between IgG and IgM antibodies against rubella virus by the immunofluorescence method.

In immunoglobulin fractions or after elimination of IgG by absorption the immunofluorescence test for rubella IgM antibodies is more sensitive than in whole serum. Blocking of IgM activity by IgG antibodies was eliminated when the time of incubation of the serum with virus antigen was prolonged. After prolonged incubation higher titres of rubella antibodies were also obtained in the IgM immunoglobulin fractions. Protein A in Staphylococcus aureus suspension effectively absorbs antibodies of IgG class. The IgM antibody titres in absorbed sera of patients infected with rubella were in some cases 2 to 4 times higher than in unabsorbed sera.     

A Socio-Demographic Examination of Adults Responding to Governmental Vaccination Recommendations during the Japanese Rubella Outbreak of 2013

Background

In 2013 a rubella outbreak occurred among Japanese people of working-age which resulted in 14,357 reported cases. The Japanese government subsequently recommended voluntary vaccination or rubella antibody testing for young women (15–49 years of age) who were planning to conceive and for adult men, children, and other persons in potential contact with pregnant women at home. However, the expense and time involved for vaccination, antibody testing and visiting a clinic may represent a major barrier to voluntary compliance among this busy demographic. The aim of the current study was, therefore, to examine potential relationships between the social background of Japanese working-age individuals affected by the 2013 voluntary vaccination campaign.

Methods

A web-based survey of 1,889 Japanese men and women aged 20–49 years was conducted in early 2014. Statistical analyses were used to explore the associations between social background and testing for rubella antibody and / or vaccination uptake during the previous year.

Results

Twenty-four percent of respondents who were planning a pregnancy had been tested for rubella antibody or vaccinated in 2013. However, among those without a current desire for pregnancy, 3% of men and 7% of women, respectively, were tested or vaccinated. Regardless of whether they were planning to conceive, testing for rubella antibodies or vaccination was statistically associated with having acquaintances who had been vaccinated, understanding the government recommendations, and being able to confirm their lack of rubella vaccination history using Maternal and Child Health Handbook records in both men and women.

Conclusion

To help eliminate rubella in Japan, additional initiatives need to target Japanese individuals who cannot envisage a direct benefit from vaccination. The results of this study suggest that disseminating the government recommendation to all potentially affected subpopulations, along with maintaining life-time vaccination records might offer a solution to encourage vaccination uptake among working-age adults in Japan, as elsewhere.     

Family Rubella Study in Los Angeles

A prospective study was initiated before the expected rubella epidemics in 1964 and 1965 in Los Angeles. Seventy-six families were evaluated by means of rubella complement fixing (cf) antibodies. The cf test, which has notable limitations, was chosen as a serologic test because it was possible to secure repeated samples of sera from all members of the families if venipuncture could be avoided.Definite evidence of clinical or serological rubella occurred in 13 of 399 persons enrolled in 1964, an attack rate of 3.3 percent. Four persons had clinical rubella only, five had clinical disease with seroconversion and four had seroconversion only. The ratio of apparent to unapparent disease was nine to four.There were four key families, each of which had more than one individual with definite clinical or serological evidence of rubella, suggesting that clustering of rubella cases does occur in families having an index case. In these families three types of intra-family spread were demonstrated: (1) all affected members had clinical disease, (2) all those affected had only inapparent disease, and (3) both apparent and inapparent disease in the same family.     

应用ELISA法检测风疹病毒IgG抗体

实验证明,将0.1％脱氧胆酸钠制备的风疹病毒粗制抗原,用于ELISA法检测风疹病毒IgG抗体,效果较满意,方法的特异性好,与常规血凝抑制试验(HI)的相关性也好,所测抗体的几何平均值为HI的4倍。用本法初步调查了北京市不同年龄人群的风疹感染率,证明随年龄增长风疹感染率迅速上升,18岁以上人群达94％。检测河北省沧州地区孕妇的风疹IgG阳性率为99％。用於风疹病人的血清学诊断,获得较好结果。     

Rubella Hemagglutination Inhibition: Removal of Nonspecific Agglutination Due to Manganous Chloride

Nonspecific inhibitors of rubella hemagglutination can be removed by treatment of sera with heparin-manganous chloride for use in the hemagglutination-inhibition test. After removal of nonspecific inhibitors by this procedure, an excess of manganous chloride may remain. This may cause the cells to agglutinate, thus obscuring the reading at low serum dilutions. This disadvantage can be overcome by the addition of sodium carbonate, which forms an insoluble compound with manganous chloride and does not interfere with antibody determination. The procedure presents a further refinement of the hemagglutination inhibition test for rubella by increasing specificity and sensitivity; it permits detection of antibody levels as low as 1:4 in sera.     

Viremia in a Recipient of HPV-77 Rubella Virus Vaccine

A live rubella virus vaccine, HPV-77 (High Passage Virus - 77 tissue culture passages) was administered subcutaneously to eight rubella-susceptible children housed in an isolation ward. One blood specimen, taken on the tenth day after vaccination, from one of the eight vaccines, yielded a rubella virus. This virus had laboratory markers which were “vaccine-like.” To our knowledge, this represents the first isolation of rubella virus from the blood of a recipient of HPV-77 vaccine. However, the consistent antibody responses among vaccinees and the regular presence of rubella virus in their pharynges argue that viremia occurs in almost every susceptible recipient. The most logical explanation for the failure to document viremia in other recipients of HPV-77 vaccine is that the viremia is ordinarily low grade or transient or both.