Wild Rubella Virus Research Articles

Seroprevalence of rubella among pregnant women in Khartoum state, Sudan

Rubella vaccine is not included in the Sudanese national immunization programme, and data on prevalence of rubella among women of childbearing age are inadequate. The objective of this cross-sectional study was to determine the seroprevalence of rubella among pregnant women in Khartoum state, Sudan. A total of 500 pregnant women who visited 7 antenatal clinics from November 2008 to March 2009 were examined for the presence of rubella IgG antibodies using ELISA. Rubella IgG antibodies were detected in 95.1% (95% Cl: 93.2%-97.0%) of women. This seroprevalence was significantly associated with education level, but not with age, residence area, occupation or parity. We presume this high seroprevalence indicates a high circulation of wild rubella virus in Khartoum state. Similar studies in other Sudanese states would be important for informing a decision to introduce rubella vaccine to Sudan.

Antenatal rubella serosurvey in Maputo, Mozambique

To describe the epidemiology of rubella in Mozambique. Cross-sectional serosurvey of rubella IgG antibodies among women attending antenatal clinics in Maputo in February-April 2002 to assess the prevalence and titres. Rubella IgG antibodies were detected in 95.3% (95% confidence interval 94.0%-96.6%) of 974 pregnant women. Age and residence did not significantly affect the prevalence of rubella IgG antibodies. However, the mean titre of rubella IgG antibodies was higher in women <20 years of age than in women > or =30 years of age (P < 0.01), and women living in urban areas had higher antibody titres than those living in suburban areas (P < 0.0001). The seroprevalence of rubella IgG antibodies among pregnant women in Maputo is high. Whether this is due to recent exposure to wild rubella virus or to exposure to rubella virus earlier in life is unclear. Studies on the burden of congenital rubella syndrome could address this matter.

Specific IgG 1 avidity maturation after rubella vaccination: A comparison with avidity maturation after primary infection with wild rubella virus

Rubella reinfection, which can affect the developing foetus, is said to occur more frequently among people who have received rubella vaccine than among those whose rubella immunity is the result of a natural infection. We have compared the rate of increase in avidity of rubella-specific antibody in these two groups since differences either in the ability of the immune response to mature or in the rate at which it matures might be attributable to differences in antigen handling during the two modes of infection. Any differences in the type or the rate of maturation might then be responsible, at least in part, for the apparent increased susceptibility of vaccinees to reinfection. Although there was evidence to suggest that there was a slightly slower maturation rate at the later stages of the immune response among the vaccinees, the number of corresponding sera from cases of natural infection, taken several months after onset of symptoms, was insufficient to allow this to be demonstrated statistically. A larger, longitudinal study would be required to establish conclusively whether a true relationship between avidity maturation and an increase in reinfection rate among vaccinees exists.

Rubella in guipuzcoa (Basque Country, Spain) a four-year serosurvey

Since the early 1980s, Spain has practiced mass vaccination of preschool children and selective vaccination of prepubertal girls. Estimated vaccination coverage in the province of Guipúzcoa (Basque Country) in recent years is about 95% (confirmed minimums of 89% for preschool children and 87.5% for 11 to 12 year-old girls). From the seroepidemiological study we could deduce that there was extensive circulation of wild rubella virus until recently (72-75% of unvaccinated girls 10 to 11 years-old had rubella antibody). More than 98% of the population at risk, represented in this study by 13,564 women (67% of all who bore children over a four-year period), possessed rubella antibodies. In the course of the study period the number of subjects (puerperal women and children) susceptible to infection declined. In spite of this favorable situation, the seroepidemiological study disclosed certain gaps that should be corrected to meet the targets for the European Region of the Expanded Programme on Immunization, and to achieve the goal of elimination of wild rubella virus in the area.

Rubella-Specific IgM in Reinfection and Risk to the Fetus

A case of reinfection with the wild rubella virus in the 8th gestational week is reported. The patient had preexisting hemagglutination inhibition antibodies of low titer following immunization with rubella vaccine. Reinfection was accompanied by clinical symptoms and the presence of rubella-specific immunoglobulin M (IgM) of high titer. Following termination of pregnancy no rubella virus could be isolated from the fetal tissues and the fetal blood contained no specific IgM antibodies. These results should encourage the use of cordocentesis before decision on interruption of pregnancy.

Immune responses to wild and vaccine rubella viruses after rubella vaccination.

Antibody responses to individual structural proteins (E1, E2, and C) of the M33 wild rubella virus and the RA 27/3 live attenuated rubella strain were assayed by immunoblotting in 11 girls, following immunization with RA 27/3 rubella vaccine. Serum samples were drawn before immunization and at 10 days, 1 month, 1 year, 2 years, and 3 years afterwards. All the subjects showed antibodies to E1 glycoprotein of both the virus strains up to three years after immunization, indicating the importance of E1 in immunity. Antibodies to E1 were always present when with neutralizing activity was observed. Antibodies to E2 protein of both the viruses and to the C protein of the M33 virus gradually disappeared with time in some samples, while antibodies to C protein of the RA 27/3 virus strain were found persistently in all the sera.

Antibody response to wild rubella virus structural proteins following immunization with RA 27/3 live attenuated vaccine.

Antibody response to individual structural proteins (E1, E2, and C) of the M-33 wild rubella virus strain was assayed by an immunoblot technique in 12 girls, following immunization with RA 27/3 live attenuated rubella vaccine. Of the 12 immunized subjects, before vaccination 9 had no demonstrable rubella specific antibodies while the remaining 3 had a low level of rubella specific antibodies, reacting only with the E1 protein. At one month after vaccination all the immunized subjects presented anti-E1, anti-E2, and anti-C specific antibodies. However, at 1-2 weeks after vaccination the 9 girls who were seronegative before immunization still had no detectable antibodies to any of the rubella virus structural proteins, while the 3 subjects whose preimmunization sera had reacted with the E1 protein presented an accelerated immune response, showing anti-E2 and anti-C specific antibodies and a more intensely marked anti-E1 specific band.

Effect of selective vaccination on rubella susceptibility and infection in pregnancy.

The effect of school and adult vaccination on susceptibility to rubella in women of childbearing age was assessed in the Manchester area, where the population attending antenatal clinics is over 40 000 a year. Between 1979 and 1984 the proportion susceptible fell from 6.4% to 2.7%. In 1984, 4.2% of nulliparous women were susceptible compared with 1.4% of women in their second or subsequent pregnancy. Eighty five per cent of pregnant women screened and found to be non-immune were vaccinated post partum before leaving hospital. Requests for prevaccination screening of non-pregnant women increased in response to a national campaign and at the time of local outbreaks of rubella but only two thirds of those found to be nonimmune were subsequently vaccinated. During 1983 and 1984 infection was confirmed in 57 pregnant women--2% of those non-immune. Selective vaccination has reduced susceptibility to rubella in the childbearing population, but it is suggested that mass vaccination of children of both sexes should be added to the existing policy to control circulation of wild rubella virus and reduce the risk of infection to pregnant women who remain susceptible.

Duration of Immunity After Rubella Vaccination: A Long-Term Study in Switzerland

In Switzerland 319 of 594 young women seronegative for rubella antibody vaccinated at 15-25 years of age against rubella with the Cendehill vaccine strain were retested 15 years later with three tests (hemagglutination inhibition, enzyme-linked immunosorbent assay, and a neutralization technique) for the presence of rubella antibodies. For 307 women rubella antibodies were still detectable by all three techniques. For nine women rubella antibodies were demonstrable by only one or two tests. Only three vaccinees were seronegative by all three tests. These three women also showed no booster response after challenge with the vaccine strain. The high percentage of women with persistent rubella antibodies 15 years after vaccination might be explained in part by the presence of subclinical reinfections due to a wild rubella virus.

The susceptibility of the postpartum and postabortal cervix and uterine cavity to infection with attenuated rubella virus

To determine the susceptibility of the postpartum and postabortal genital tract to infection with attenuated rubella virus, 30 patients with negative hemagglutination inhibition (HI) titers were studied. Following inoculation with Cendehill or RA 27/3 vaccine, viral cultures of the cervix and uterine cavity were obtained with blood specimens to evaluate serologic conversion. Attenuated rubella virus was not isolated in any patient; seropositive conversion was achieved in 24 women. The significance of these findings related to wild rubella virus infection is discussed.

GESTATIONAL EXPOSURE TO RUBELLA VACCINEES.A POPULATION SURVEILLANCE STUDY

FLEET, WILLIAM F.; VAUGHN, WILLIAM; LEFKOWITZ, LEWIS B. JR.; SCHAFFNER, WILLIAM; FEDERSPIEL, CHARLES F.; THOMPSON, JULIETTE; KARZON, DAVID T. Author Information

Controlling rubella: problems and perspectives.

Long-term effectiveness of rubella vaccination in childhood is of particular importance because the ultimate goal of immunization is the prevention of infection during pregnancy. To determine how well vaccine-induced immunity persists in comparison to that acquired naturally, several hundred susceptible children who seroconverted after receiving HPV77DE5 vaccine were followed serologically over a 3-to-5-year period. The results indicate that vaccine-induced antibodies are less stable than those acquired through natural infection, and their persistence is closely related to the original response to immunization. Thus children who responded with a broad range of antibody types and who had brisk postvaccinal hemagglutination-inhibiting antibody titers of greater than or equal to 1:64, maintained such levels without significant decline. In contrast, among the children who had feeble hemagglutination-inhibiting antibody responses initially and failed to develop complement-fixing or precipitating antibodies, a significant proportion lost detectable hemagglutination-inhibiting antibody levels after 3 to 5 years. The current and future immunity of such children is therefore in doubt, unless natural reinfection with wild rubella virus or revaccination with a more effective vaccine corrects their antibody deficiencies.

Gestational exposure to rubella vaccinees: a population surveillance study.

Over a two-year period an attempt was made to identify instances of transmission of rubella vaccine virus from rubella vaccinees to pregnant women in Nashville-Davidson County, Tennessee. Approximately 24,000 children were immunized in a mass campaign at the outset of the study. Several prospective surveillance methods of 11,635 women and their new babies were employed. Attempts were made to recover rubella virus from throat swabs of 10,951 newborns. No rubella vaccine virus was recovered. Wild rubella virus was isolated from a single infant with the congenital rubella syndrome whose mother had natural rubella during the first month of pregnancy. Rubella virus was not isolated from the products of 240 abortions. There were no seroconversions among 3990 women who had paired sera available for study. Clinical and serologic follow-ups of infants judged to be a high risk because of intimate maternal exposure to vaccine virus revealed no late manifestations of congenital rubella infection. A history of close maternal contact with vaccinees during the three months before and the three months following conception was not associated with an increased incidence of congenital anomalies or clinical features seen with congenital rubella infection. Thus, no evidence of vaccine virus transmission was found, providing further evidence of the safety of rubella vaccine under field conditions. A seroepidemiologic study of 8824 pregnant women revealed the expected decline in rubella susceptibility with increasing age. When age was controlled, the variables of race, parity, and educational achievement produced no major influence on immunity.

Rubella and the Fetus

<h3>To the Editor.—</h3> In the article "Inadvertent Rubella Vaccination of Pregnant Women" (225:1472, 1973) the authors conclude that the evidence "strongly suggests that RVV poses a definite hazard to the fetus." This conclusion is based on histopathologic similarities between the RVV and the wild rubella virus in abortion specimens. If this thesis is brought to its logical conclusion, then 10% to 50% of the 11 seronegative women plus a percentage of the 85 unknown mothers (some of the 85 had to be previously seronegative) should have given birth to babies with rubella defects, yet there was not a single rubella abnormality among the 96 live births. The evidence suggests the opposite conclusion to me—that RVV may be incapable of causing clinical rubella. The virus was isolated from seven of 119 abortion specimens. If looked for, other viruses might be found as well in a sample of abortion specimens, with some

BOOSTER IMMUNIZATION AGAINST RUBELLA IN ADULT WOMEN

Twenty-three seronegative women living in a mental institution were immunized with Cendehill rubella vaccine. Five others without antibody to rubella who resided in the same quarters were not immunized and served to monitor the possible introduction of wild virus into the institution. All those who received the vaccine developed significant antibody titers. Nine months following the initial vaccination, ten women were given a booster dose of vaccine; none showed an increase in antibody titers. Twenty-two months after primary immunization, the other 13 were reimmunized; only one exhibited a response. The incidence of a booster effect for the group as a whole was only 4.4%. None of the unvaccinated seronegative individuals developed specific antibody, indicating a lack of introduction of wild rubella virus into the environment.

Inadvertent Rubella Vaccination of Pregnant Women

Two hundred fifteen cases of inadvertent rubella vaccination in early pregnancy or shortly before conception have been studied to determine the risk of fetal infection with rubella vaccine-like virus (RVV). Of the 215 women, 184 (86%) did not have prevaccination sero-immunity screening. Only 24 women (11%) were known to be susceptible prior to vaccination. One hundred seven (50%) of the pregnancies ended with induced abortions, 12 (5%) with spontaneous abortions, and 96 (45%) with live births. None of the live-born infants had serologic or clinical evidence of congenital rubella; however, RVV was isolated from abortion specimens in seven cases, three of which had isolates from fetal tissue. The similarities between RVV and wild rubella virus infection of decidual, placental, and fetal tissue strongly suggest that RVV poses a definite hazard to the fetus.

Experience with rubella and rubella immunization in institutionalized children

Serial monitoring of rubella hemagglutination-inhibiting antibodies in institutionalized children revealed that 4 of 16 nonvaccinated rubella-susceptible children had developed antibodies and 4 of 29 children immunized with Cendehill rubella vaccine had a fourfold or greater rise in antibody titer during the same 4 year interval. This apparent spread of wild virus occurred within three building with a population estimated to be 91 per cent “immune.” The vaccinees have shown a slight fall in hemagglutination-inhibiting antibody titers over the four years, and both the vaccines and naturally immune children who experienced the “booster” response had titers lower than the others. These observations cast doubt on the ability of “herd immunity” to prevent the spread of wild rubella virus.

Booster immunization against rubella in adult women

Twenty-three seronegative women living in a mental institution were immunized with Cendehill rubella vaccine. Five others without antibody to rubella who resided in the same quarters were not immunized and served to monitor the possible introduction of wild virus into the institution. All those who received the vaccine developed significant antibody titers. Nine months following the initial vaccination, ten women were given a booster dose of vaccine; none showed an increase in antibody titers. Twenty-two months after primary immunization, the other 13 were reimmunized; only one exhibited a response. The incidence of a booster effect for the group as a whole was only 4.4%. None of the unvaccinated seronegative individuals developed specific antibody, indicating a lack of introduction of wild rubella virus into the environment.

Booster Immunization Against Rubella in Adult Women

Twenty-three seronegative women living in a mental institution were immunized with Cendehill rubella vaccine. Five others without antibody to rubella who resided in the same quarters were not immunized and served to monitor the possible introduction of wild virus into the institution. All those who received the vaccine developed significant antibody titers. Nine months following the initial vaccination, ten women were given a booster dose of vaccine; none showed an increase in antibody titers. Twenty-two months after primary immunization, the other 13 were reimmunized; only one exhibited a response. The incidence of a booster effect for the group as a whole was only 4.4%. None of the unvaccinated seronegative individuals developed specific antibody, indicating a lack of introduction of wild rubella virus into the environment.

A clinical and serological study of women exposed to rubella vaccinees.

Five hundred thirty-five women living in Utah were evaluated serologically before and after a rubella immunization campaign in April 1970. Sixty-one percent of these women were pregnant. Of 33 susceptible women with household contact to vaccine recipients, one developed serologically documented rubella; however, the antibody response suggested that this illness was caused by wild rubella virus. None of 52 seronegative women without household contact to vaccinees became seropositive. One of 450 previously immune women had a fourfold rise in rubella antibody. These findings support the concept that infection of a susceptible adult with vaccine virus secondary to spread from a vaccinee is an unlikely event.