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.     

Surveillance of antibody to rubella virus in Grampian: closing the immunity gap.

OBJECTIVES--To identify causes for the continuing deficit of rubella immunity in women of childbearing age with a view to further reducing the risk of the congenital rubella syndrome. DESIGN--A questionnaire was sent to the general practitioner and a laboratory follow up study conducted in a one year cohort of women found on screening to have inadequate protection against rubella. SETTING--Virus laboratory of the department of medical microbiology, Aberdeen, serving the health board areas of Grampian, Orkney, and Shetland. PATIENTS--239 women whose concentration of antibodies to rubella virus was either absent or below standard (15,000 IU/l) and whose general practitioner could be contacted to supply a history of infection, immunisation, pregnancy, and antibody testing. MAIN OUTCOME MEASURES--Whether rubella vaccination was given and whether those vaccinated were tested for seroconversion. RESULTS--Only 122 (55%) of the women for whom information was available received the recommended vaccine; only 74 (61%) of these were tested for seroconversion. Oversight was the reason given for not vaccinating 64 (65%) of the women who remained at risk. Women who were pregnant when tested were significantly less likely to receive vaccine (odds ratio 3.36) than women who were not pregnant, and even if vaccinated were less likely to have a follow up antibody test (odds ratio 1.94). CONCLUSION--Once women are identified as being unprotected against rubella they are often overlooked and not vaccinated. Prompting mechanisms aimed at general practitioners, such as the one recently set up in Grampian, should reduce the immunity gap and help to eradicate rubella in pregnancy.     

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.     

Effect of rubella vaccination programme in schools on rubella immunity in a general practice population.

Between November 1979 and January 1980 all patients aged 13-21 years who attended a general practice in Glasgow were tested for their immunity against rubella (single radial haemolysis test). All of the women in the sample should have been vaccinated at 13 as part of the rubella vaccination programme, which began in Glasgow in 1971. The programme excludes boys. Of the 77 females and 64 male patients studied, nine (11.7%) and 10 (15.6%), respectively, were susceptible to the infection. For only 34 women was evidence of vaccination documented in the practice records, and three of those either had failed to seroconvert or had antibody below detectable values. Overall there was no significant differences between the proportion of men and women who were susceptible to the disease. The rubella vaccination programme had clearly failed to reduce the number of susceptible women in this practice. Hence the immune state of all girls should be checked at about 15 years of age, so that as many as possible may be rendered immune before they leave school.     

An error in Rh testing in pregnancy.

Anti-D (anti-Rho) in the blood of two Rh-negative pregnant women was believed to be due to active immunization. In the first case, however, antibodies were no longer detectable 2 weeks later. In the second case they disappeared by the end of 31 weeks. It was discovered that both women had been given immune globulin (human) because of exposure to rubella. The globulin given to the first woman probably contained about 0.1 mug of anti-D per ml; that given to the second probably contained about 0.6 mug of anti-D per ml. Both babies were O Rh-positive. Both women were given Rh immune globulin after delivery. Both have completed a further pregnancy and no anti-D has been found on many tests. In tests carried out in 1971 all samples of immune globulin (human) examined contained anti-D, but usually in inconsequential trace amounts.     

Prevalence of HIV antibody and pregnancy in Tayside, 1984-9: background to screening.

OBJECTIVE--To determine age specific prevalence of HIV antibody, incidence of pregnancy, and likelihood of detection and correct assignment to risk category by antenatal screening of women known to be positive for HIV antibody, from 1984 to 1989. DESIGN--Retrospective analysis of reproductive history and risk behaviour of women positive for HIV antibody and prediction of detection by screening on the basis of blood group samples, Guthrie tests, and rubella tests. SETTING--City of Dundee, where the prevalence of HIV is high, since the appearance of HIV in 1984, predominantly among heterosexual intravenous drug users. PATIENTS--All (61) women known to be positive for HIV antibody who had had clinically indicated tests, for whom case notes were available for 60. MAIN OUTCOME MEASURES--Risk assessment according to case notes and reported to the laboratory, incidence of infection, geographical location, age, date of positive test result, and reproductive history. RESULTS--With 61 infected women the overall minimum prevalence among women within the city of Dundee was 0.67/1000 and 2.9/1000 among women in their third decade. Of the 60 women whose reproductive history was available, 35 had 57 pregnancies, 36 of which occurred after seroconversion was known to have taken place, representing 8.7% of the total number of affected pregnancies reported for the United Kingdom. If antenatal screening for HIV had been performed between 1984 and 1989 it could not have detected positivity for HIV antibody in 25 (42%) women who had no pregnancies during this time. Among the remaining 35 women, screening samples taken for blood grouping could have identified a maximum of 34 (57%), samples taken to check rubella susceptibility a maximum of 22 (37%), and blood spots on Guthrie cards a maximum of 19 (32%). Retesting would have occurred in 14 women 33 times with samples taken for blood grouping, but three and four women would have been tested twice using samples taken for rubella testing and Guthrie cards respectively. Anonymous screening would have been unable to determine risk category as a history of intravenous drug use was known in 47 (79%) women before testing but this was increased by a further 5 (8%) who admitted to it after the test result was known. CONCLUSION--Interpreting the results of antenatal screening programmes will be complex and will underestimate overall prevalence of HIV antibody among women; this will be exaggerated by strategies based on anonymous testing with Guthrie cards or on samples taken for rubella testing, which do not include women who have had an earlier loss of pregnancy. Only open testing with consent will permit satisfactory attribution to     

Is there a link between blastomere contact surfaces of day 3 embryos and live birth rate?

Background

Limitations in our current knowledge of normative physiologic changes in thyroid function during the periconception window narrow our ability to establish an optimal approach to screening and diagnosis of thyroid disease in pregnant women. The objective of this study was to characterize changes in thyroid function during the transition from the pre-pregnant to pregnant state in normal fertile women.

Methods

Women (N = 60) ages 30-42 years without a history of thyroid disease, who were planning pregnancy, were observed prospectively before and during early pregnancy. Thyroid function (thyroid stimulating hormone, TSH and free thyroxine, FT4) was measured before conception and between 6 and 9 weeks gestation. Pre-pregnancy samples were analyzed for thyroid antibodies. Bivariate analyses and longitudinal curves (general estimating equation models) were used to analyze changes in thyroid function during the periconception window by antibody status.

Results

Pre-pregnancy TSH values were significantly higher than early pregnancy TSH (p < 0.001), but FT4 values did not differ (p = 0.53). TSH declined as gestational age increased (P < 0.01). Thyroid antibody positive women had a higher pre-pregnancy TSH compared to antibody negative women (p < 0.01). Periconceptional change in thyroid function was more variable among women with antibodies (p < 0.001). 50% of women with elevated pre-pregnancy TSH values (TSH > 3.0 mIU/L) had normal TSH values (TSH < 2.5 mIU/L) in pregnancy.

Conclusions

TSH values decline during the transition from pre-pregnancy to early pregnancy. The change in TSH appears to be less predictable in women with thyroid antibodies. Periconceptional changes in thyroid function should be considered in formulating prenatal thyroid screening guidelines.     

Persistence of naturally acquired cell-mediated immunity to rubella virus during the first trimester of pregnancy

We studied the persistence of naturally acquired cell-mediated immunity to rubella during early pregnancy. We compared lymphocyte transformation responses to phytohemagglutinin and rubella virus in 35 naturally immune women aged 17-37 years, in the first trimester of pregnancy, with 49 naturally immune age-matched nonpregnant controls. A significant lower lymphocyte transformation response to phytohemagglutinin was observed during the first trimester of pregnancy (P = 0.008), but lymphocyte transformation responses to rubella virus were not significantly different (P = 0.901). These data indicate that, in naturally immune women, cell-mediated immunity to rubella virus is not significantly altered by the physiological changes in early pregnancy.     

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.     

Absence of cell-mediated immunity to rubella virus 5 years after rubella vaccination.

The long-term effectiveness of rubella vaccination in childhood is particularly important because the ultimate goal of immunization is the prevention of infection during pregnancy. Of 25 healthy children tested 4 to 5 years after rubella vaccination, 19 showed no evidence of cell-mediated immunity (CM) to rubella virus despite the presence of hemagglutination-inhibition or complement-fixation antibodies or both. Twenty-two of 25 seropositive, naturally infected young adults showed evidence of CMI. These results indicate that fetuses of women who have been vaccinated against rubella may not be protected against damage by wild rubella infection during the pregnancy, when CMI is physiologically depressed.     

Time to Pregnancy: A Computational Method for Using the Duration of Non-Conception for Predicting Conception

An important problem in reproductive medicine is deciding when people who have failed to become pregnant without medical assistance should begin investigation and treatment. This study describes a computational approach to determining what can be deduced about a couple''s future chances of pregnancy from the number of menstrual cycles over which they have been trying to conceive. The starting point is that a couple''s fertility is inherently uncertain. This uncertainty is modelled as a probability distribution for the chance of conceiving in each menstrual cycle. We have developed a general numerical computational method, which uses Bayes'' theorem to generate a posterior distribution for a couple''s chance of conceiving in each cycle, conditional on the number of previous cycles of attempted conception. When various metrics of a couple''s expected chances of pregnancy were computed as a function of the number of cycles over which they had been trying to conceive, we found good fits to observed data on time to pregnancy for different populations. The commonly-used standard of 12 cycles of non-conception as an indicator of subfertility was found to be reasonably robust, though a larger or smaller number of cycles may be more appropriate depending on the population from which a couple is drawn and the precise subfertility metric which is most relevant, for example the probability of conception in the next cycle or the next 12 cycles. We have also applied our computational method to model the impact of female reproductive ageing. Results indicate that, for women over the age of 35, it may be appropriate to start investigation and treatment more quickly than for younger women. Ignoring reproductive decline during the period of attempted conception added up to two cycles to the computed number of cycles before reaching a metric of subfertility.     

Pregnant Women in and Around Dhaka City: Are Their Children at Risk of Developing Congenital Rubella Syndrome?

Rubella Virus (RUBV) is a common cause of childhood rash and fever in non-immunized populations, and its public health importance relates to teratogenic effects of primary rubella infection in women with early pregnancy. Infection of the fetus may lead to congenital rubella syndrome (CRS). This work aimed to assess the degree of risk associated in acquiring rubella virus infection by the women during pregnancy and developing CRS among their children in Bangladesh. The study population (n = 275) included pregnant mothers (15–38 years) from various socioeconomic backgrounds attending a women health care based hospital. All subjects were personally interviewed, clinically examined and a standardized questionnaire was filled up for each of them. From each participant 3 ml blood was taken and serum was separated. Commercially available ELISA kit was used for the qualitative and quantitative determination of IgM and IgG class antibodies against RUBV in collected serum samples. 209 women were found to contain detectable level of antiRUBV IgG antibodies, but did not possess IgM antibodies against rubella. Only 9% participants were vaccinated previously against rubella virus among the whole antenatal population studied. Ninety-two percent of these vaccinated pregnant women contained serum anti-rubella IgG antibody which was significantly (P = 0.05) higher than that of the nonvaccinated study population (75%). Pregnant women from lower middle and poor socioeconomic class had significantly (P = 0.05) more intra uterine growth retardation (IUGR) of fetus than the upper middle class. 20% of the women of child bearing age examined in this work were not yet exposed to RUBV and at risk of acquiring this virus during pregnancy and subsequently transmitting the virus to the fetus. Our work demonstrates rubella attack rate among antenatal population in Bangladesh as 14.5 in 1000 during pregnancy. A proper and reliable vaccination policy against rubella virus is not yet adopted at the national level in many developing countries including Bangladesh. This work identifies the requirement of detailed study for the identification of intrauterine rubella infection and its related influence on perinatal morbidity and mortality. Thorough epidemiological studies are also considered necessary prior to the development and acceptance of national immunization program against rubella virus in Bangladesh.     

Avidity of immunoglobulin G to rubella virus in post-vaccination and post-infection immunity

Comparative evaluation of avidity of IgG to rubella virus in vaccinated persons, in patients with rubella or other exanthematous illness, and in healthy persons revealed similar patterns in post-vaccination and post-infection immunity. Virus specific low avidity IgG (index of avidity < or =30%) were detected in patients with rubella during 7 weeks after symptoms appeared as well as in vaccinated persons which were tested 6 weeks after vaccination. Low avidity antibodies in sera were detected in 96% of patients with rubella and in 75% of vaccinated persons which were not immune before immunization. Live attenuated vaccines Ervevax, Priorix, and MMR-II had similar ability to induce low avidity IgG to rubella virus. Increase of low avidity antibodies concentration was noted after immunization of children with low levels of antibodies before vaccination. After immunization of persons with high avidity antibodies in serum, index of avidity remained above threshold. Anamnestic high avidity IgG (index of avidity 51-100%) were detected in majority of immune healthy persons (96.4%) as well as in patients with exanthematous illnesses not related to rubella infection (93.6%). ELISA test-systems for detection of low avidity IgG to rubella virus allow to obtain reliable information about seroconversion rate and characteristics of immune response in vaccines. Detection of low avidity IgG in serum obtained 5-6 weeks after immunization points to primary immune response, whereas identification of high avidity antibodies reveals already immune persons.     

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.     

Rubella Epidemic in a Maternity Unit

Four cases of rubella, the last confirmed by laboratory tests, occurred among the nurses of a large obstetric unit. Immediate measures were taken to prevent the spread of the infection to pregnant patients and staff, and none was in fact infected.Persons susceptible to rubella and who become infected may pose a real danger to women in early stages of gestation during the incubation period. We recommend that the immune status of medical and nursing personnel working in obstetric departments should be ascertained serologically, and that rubella vaccine should be offered to those who are susceptible.     

Vitamin A,Pregnancy, and Oral Contraceptives

It has been shown that women receiving oral contraceptives have increased levels of serum vitamin A. High vitamin A levels may constitute a teratogenic hazard and it has been suggested that women who conceive soon after discontinuing oral contraceptive therapy may be especially at risk to this hazard.We have confirmed a significant increase in vitamin A levels in women taking oral contraceptives. During early pregnancy there is no significant difference in vitamin A levels between women who have recently been taking oral contraceptives and those who have not. We have been unable to show that either taking oral contraceptives shortly before pregnancy or a high vitamin A level during the first trimester of pregnancy, comparable to that of a woman taking oral contraceptives, has any detrimental effect on the outcome of pregnancy. It seems unlikely that women who conceive soon after discontinuing oral contraception run any teratogenic risk from increased vitamin A levels.     

Compliance with postpartum Rh isoimmunization prophylaxis in Alberta

A retrospective review of obstetric records for 1979 in two major Calgary hospitals was undertaken to determine the rate of compliance with postpartum Rh isoimmunization prophylaxis in Alberta. The charts of 4528 women ranging in age from 13 to 46 years were reviewed. The prevalence rate of Rh negativity was found to be 16%. Of the 710 Rh-negative women 490 (69%) were eligible to receive Rh immune globulin (RhIG); that is, they had no anti-D antibodies, and the baby/fetus was Rh-positive or Rh-unknown. RhIG had been administered to 93.6% of the eligible women; the compliance rate ranged from 66.7% for obstetric emergencies (i.e., spontaneous abortion, antepartum or early-pregnancy hemorrhage, or ectopic pregnancy) to 98.2% for postpartum diagnoses. In more than half (54.7%) of the women who underwent amniocentesis Rh type was not determined; the implications of this finding are discussed. Although poor compliance with postpartum RhIG administration is not a reason for withholding antepartum administration of RhIG, maximum compliance with the more cost-effective programs should be attained before antepartum programs are fully implemented.     

Congenital rubella in babies of south Asian women in England and Wales: an excess and its causes.

The incidence of congenital rubella was found to be 2.3 times higher in Asian than non-Asian births in England and Wales. This was attributed in part to higher susceptibility to rubella in Asian than non-Asian women, as shown by antenatal serological data from public health laboratories in Leeds, Luton, and Manchester. Examination of the ethnic origin of pregnant women requesting laboratory testing after contact with rubella or rash and of women with laboratory confirmed rubella in pregnancy also suggested that the disease was being underdiagnosed in pregnant Asian women. Failure to prevent congenital rubella by termination of infected pregnancies may therefore contribute to the increased incidence of the syndrome in Asians. Health education programmes about the dangers of rubella in pregnancy and of the need for vaccination can readily be promoted in the Asian community through existing ethnic organisations. Protection of other ethnic minorities likely to be at similar increased risk may require a vaccination programme aimed at national elimination of rubella.