How to prevent rubella epidemics and congenital rubella syndrome: lessons from 42 years of longitudinal epidemiology in Osaka Prefecture, Japan (1982-2023).

BACKGROUND: Despite the introduction of rubella-containing vaccine into routine immunization in 1977, rubella has not been eliminated in Japan. This study aimed to validate the immunization strategy and to highlight the crucial elements of elimination program. METHODS: We scrutinized cases of rubella and congenital rubella syndrome (CRS). Additionally, we analyzed the national vaccination coverage, seroprevalence, and number of maternal rubella-related spontaneous or artificial fetal deaths. RESULTS: The shift from selective to universal immunization significantly reduced rubella cases coupled with increased seroprevalence in children. However, rubella resurged in 2012-2013 and 2018-2019, which was virologically and serologically confirmed to be associated with imported rubella virus (RuV) and susceptible males. Although the disease burden of CRS may have been suppressed in the past by the large number of spontaneous or artificial fetal deaths, the incidence rate of CRS was comparable to that of the 1960s to 1980s. Cases of breakthrough infection and CRS were identified in females who were considered to have a history of single-dose vaccination. CONCLUSIONS: Even with universal immunization, future epidemics and severe outcomes cannot be prevented unless immunization gaps are closed. Furthermore, CRS and breakthrough infection are not completely prevented by single-dose vaccination, indicating the need for second-dose vaccination.

Rubella transmissibility and reproduction number (Ro): A critical appraisal of the prospects for its control in Nigeria.

Rubella is a highly contagious disease of public health importance that is endemic in Nigeria. Rubella with its devastating sequel, congenital rubella syndrome, is a neglected disease with no surveillance system in place and no national incidence figure in Nigeria. This article, therefore, seeks to do reviews of rubella transmissibility, its reproduction number and the prospects for its control in Nigeria. This is a review of literatures with triangulation of findings along the objectives and the use of available secondary data to analyse the prospects of rubella control in Nigeria. Data were analysed and presented with appropriate tables and charts. A number of factors can fuel rubella transmission causing increase in reproduction number, Ro.The high birth rate, poor rubella surveillance and non-inclusion of rubella vaccines in the routine vaccination schedule among others are some of the factors working against a good outlook for rubella control in Nigeria. The Nigerian government should control the growing population, ensure a robust surveillance for rubella and incorporate rubella-containing vaccine in the immunisation schedule for infants with regular vaccination campaigns for older children and adults.

Vaccination in secondary school students expedites rubella control and prevents congenital rubella syndrome.

BACKGROUND: In order to control the spread of rubella and reduce the risk for congenital rubella syndrome, an additional rubella vaccination program was set up for all secondary school students since 2008 in Zhejiang, China. METHODS: We conducted a descriptive analysis of rubella incidence among different age groups from 2005 to 2015 and a serosurvey of female subjects aged 15-39 years to understand the possible effects of this immunization program. RESULTS: The average annual rubella incidence rate had decreased from 15.86 per 100,000 population (2005-2007) to 0.75 per 100,000 population (2013-2015) in Zhejiang. The decrease in the rate of rubella incidence in girls aged 15-19 years was more accelerated (from 138.30 to 0.34 per 100,000) than in the total population during 2008-2015 (from 32.20 to 0.46 per 100,000). Of 1225 female subjects in the serosurvey, 256 (20.9%) were not immune to rubella. The proportion of subjects immune to rubella was significantly different among different age groups (Wald χ2 = 22.19, p = 0.000), and subjects aged 15-19 years old had the highest immunity (88.0%). Rubella antibody levels were significantly lower in women aged 25-30 years with 26.7% of them not immune, followed by the group aged 20-24 years (25.0%) and 30-35 years (24.5%). CONCLUSIONS: Rubella vaccine included in the Expanded Program on Immunization together with vaccination activities for secondary school students can help in rubella control, particularly in targeted age groups in the program. Seroprevalence of antibodies to the rubella virus amongst the female population within childbearing age in Zhejiang, China, is still too low to provide immunity. In addition to vaccination programs in the secondary schools, rubella vaccination should also be encouraged in women of childbearing age, which can be done effectively combined with pre-marital examination in China.

Acceptance of Rubella-Containing Vaccine and Factors Associated with Acceptance among Women of Reproductive Age in China: A Cross-Sectional Study.

Objectives: To investigate the acceptance and factors influencing acceptance of rubella-containing vaccine (RCV) among women of reproductive age in Guangdong, Henan, Hubei, Liaoning, Shanxi, Sichuan and Zhejiang provinces of China. Methods: Using a stratified sampling method, we selected one urban and one rural community health services center in each of two cities in seven provinces. From these centers, we recruited women 15-49 years of age to complete a questionnaire on their willingness to receive RCV and factors influencing willingness. The survey instrument was adapted from the behavioral and social drivers (BeSD) of vaccination survey tool developed by the World Health Organization. Results: Among 1286 participants, 981 (76.3%) were willing to receive RCV. Awareness of rubella ranged from 12.4% to 70.6%. Willingness to receive RCV differed significantly by region, occupation, vaccination history, and awareness. All latent variables of the structural equation model (SEM) were positively correlated with willingness, and all standardized paths were statistically significant (p < 0.001). Thinking and Feeling had direct positive effects on Social Processes (ß = 0.789) and Practical Issues (ß = 0.542), thereby indirectly affecting motivation. Conclusions: Women of reproductive age had high willingness to receive the rubella vaccination, but their general awareness of rubella was relatively low. It is necessary to strengthen the health education of women of reproductive age regarding rubella to improve RCV coverage.

Comparison of Congenital Rubella Syndrome Cases at a Philippine Tertiary Hospital from 2009-2012 to 2019-2022.

Background and Objective: The Philippines does not have a national congenital rubella syndrome (CRS) surveillance or registry. Regular monitoring of CRS cases in hospitals, including in a Philippine tertiary hospital, helped in the past to provide clinico-epidemiologic data on CRS. This study aimed to continue providing clinico-epidemiologic data on CRS cases seen in the Philippine tertiary hospital from 2009-2012 and 2019-2022 and compare the cases seen from said timelines. Methods: A cross-sectional study was used, employing chart review of patients newly diagnosed with CRS from 2009-2012 and 2019-2022 in the Department of Ophthalmology and Visual Sciences at the Philippine tertiary hospital. Results: Forty-two patients newly diagnosed with CRS from 2009-2012 and 2019-2022 were included. Only 14 (33%) were serologically-confirmed cases (albeit qualitatively). Median age (first and third interquartile ranges) at consult was 1 year (0.4, 2.5). Twenty-four (57%) patients had maternal history of rashes and/or fever. Trimester of pregnancy when mother became symptomatic was not significantly correlated with chief complaint (p=0.20) and numbers of ophthalmic (p=0.68) and systemic manifestations (p=0.32). Cataract was the most common ophthalmic manifestation present in 40 (95%) patients. Twenty-six (62%) patients had other associated systemic findings of which hearing loss was the most common. Only 29 of 40 patients with cataract underwent lensectomy, with 23 patients having poor visual prognosis prior to surgery (5 with nystagmus alone, 10 with nystagmus and strabismus, and 8 with strabismus alone). Discussion: Using ophthalmic manifestations as primary indicator, this study provided an update on the CRS cases in the country. Laboratory confirmation remains a challenge in diagnosing CRS as the tests are costly and not widely available. There was increase from 2009-2012 compared to 2019-2022 in number of patients who underwent surgical treatment for cataract but visual outcomes were suboptimal due to delay in consultation. Although there was a decrease in number of CRS cases seen in the Philippine tertiary hospital, this cannot be attributed to increased rubella-containing vaccine (RCV) coverage alone. Conclusion: Provision of data from individual hospital-based studies similar to this highlights the need for a national CRS surveillance system or registry. This can better gauge the burden of CRS and identify the gap in RCV coverage.

A case of congenital rubella syndrome and epidemiology of related cases in China, 2014-2023.

Rubella is a major cause of congenital defects, and the presence of rubella infection in a pregnant woman may lead to fetal death or congenital defects known as congenital rubella syndrome(CRS). Since China has not yet established a national CRS surveillance system, the true incidence cannot be determined. To understand the disease burden and epidemiological characteristics of CRS cases in China, the article reports the first case of CRS in Quzhou, China, and conducts a retrospective analysis of related cases that have been reported in China over the past decade. Because the availability of rubella-containing vaccines (RCV) was not widespread in China before 2008, women of childbearing age born before 2008 are generally unvaccinated against RCV. Due to the lack of routine CRS monitoring and screening, CRS is underreported in China. Vaccination of nonimmune women of childbearing age with RCV and establishing a sensitive and timely case-based CRS surveillance system can accelerate the elimination of rubella and CRS.

Rubella seroprevalence among mothers and incidence of congenital rubella three years after rubella vaccine introduction in Vietnam.

Following a rubella outbreak in 2011, Vietnam implemented a mass measles-rubella vaccination campaign for children aged 1-14 years in 2014-2015, further expanding the target age to 16-17 years in 2016; routine vaccination was introduced in 2014. However, there was concern that a substantial proportion of women of child-bearing age were still susceptible to rubella, with the fear of congenital rubella emergence. Thus, we conducted a prospective cohort study in Nha Trang, Vietnam, from 2017-2018 to investigate pregnant women's susceptibility to rubella infection, the incidence of congenital rubella infection, and factors associated with susceptibility. Cord blood was tested for rubella-specific immunoglobulin M (IgM) and IgG; neonatal saliva and cord blood specimens were examined for rubella-RNA. We analyzed 2013 mother-baby pairs. No baby was rubella-IgM or rubella-RNA positive. Overall, 20.4% of mothers were seronegative (95% confidence interval, 18.6%-22.1%). The seronegativity was significantly low among mothers aged <35 years. We found that maternal age groups of 20-24 and 25-29 years, and the lack of self-reported vaccination history were significantly associated with seronegativity. Many pregnant women who were not covered by the vaccination campaign are still at risk of rubella infection.

Immunogenicity, duration of protection, effectiveness and safety of rubella containing vaccines: A systematic literature review and meta-analysis.

BACKGROUND: Rubella containing vaccines (RCV) prevent rubella virus infection and subsequent congenital rubella syndrome (CRS). To update the evidence on immunogenicity, duration of protection, effectiveness and safety of RCV, we conducted a systematic literature review. METHODS: We searched EMBASE and SCOPUS, using keywords for rubella vaccine in combination with immunogenicity (seroconversion and seropositivity), duration of protection, efficacy/effectiveness, and safety. Original research papers involving at least one dose of RCV (at any age), published between 1-1-2010 and 17-5-2019 were included. Where appropriate, meta-analyses were performed. Quality of included studies was assessed using GRADE methodology. RESULTS: We included 36 papers (32 randomized controlled trials (RCTs) and 4 observational studies) on immunogenicity (RA27/3 strain) in children and adolescent girls, 14 papers (5 RCTs and 9 observational studies) on duration of protection, one paper on vaccine effectiveness (VE) (BRDII strain), and 74 studies on safety, including three on safety in pregnancy. Meta-analysis of immunogenicity data showed 99% seroconversion (95% CI: 98-99%) after a single dose of RCV in children, independent of co-administration with other vaccines. Seroconversion after RCV1 below 9 months of age (BRDII strain, at 8 months) was 93% (95% CI: 92-95%). For duration of protection, the included studies showed a seropositivity of 88%-100% measured 1-20 years after one or two RCV doses. The single study on VE of BRDII strain, reported 100% VE after one and two doses. Among 34,332 individuals participating in the RCTs, 140 severe adverse events (SAEs) were reported as possibly related to RCV. Among the case reports on SAEs, the association with RCV was confirmed in one report (on fulminant encephalitis). Among 3,000 pregnant women who were inadvertently vaccinated, no SAEs were reported. CONCLUSIONS: One and two doses of RCV are highly immunogenic for a long period of time, effective in preventing rubella and CRS, and safe.

Rubella Vaccine Introduction in the South African Public Vaccination Schedule: Mathematical Modelling for Decision Making.

Background: age structured mathematical models have been used to evaluate the impact of rubella-containing vaccine (RCV) introduction into existing measles vaccination programs in several countries. South Africa has a well-established measles vaccination program and is considering RCV introduction. This study aimed to provide a comparison of different scenarios and their relative costs within the context of congenital rubella syndrome (CRS) reduction or elimination. Methods: we used a previously published age-structured deterministic discrete time rubella transmission model. We obtained estimates of vaccine costs from the South African medicines price registry and the World Health Organization. We simulated RCV introduction and extracted estimates of rubella incidence, CRS incidence and effective reproductive number over 30 years. Results: compared to scenarios without mass campaigns, scenarios including mass campaigns resulted in more rapid elimination of rubella and congenital rubella syndrome (CRS). Routine vaccination at 12 months of age coupled with vaccination of nine-year-old children was associated with the lowest RCV cost per CRS case averted for a similar percentage CRS reduction. Conclusion: At 80% RCV coverage, all vaccine introduction scenarios would achieve rubella and CRS elimination in South Africa. Any RCV introduction strategy should consider a combination of routine vaccination in the primary immunization series and additional vaccination of older children.

Safety profile of rubella vaccine administered to pregnant women: A systematic review of pregnancy related adverse events following immunisation, including congenital rubella syndrome and congenital rubella infection in the foetus or infant.

BACKGROUND: Data on the safety of inadvertent rubella vaccination in pregnancy is important for rubella vaccination programs aimed at preventing congenital rubella syndrome. METHODS: The association between monovalent rubella or combination vaccinations in or shortly before pregnancy and potential harm to the foetus was examined by conducting a systematic review and meta-analysis using fixed effect methods and simulation. RESULTS: Four cohort studies of inadvertently vaccinated and unvaccinated women were found, 15 cohorts of pregnant women who were rubella susceptible at time of inadvertent vaccination and 9 cohort studies with no information on susceptibility and case series. No case of vaccine associated congenital rubella syndrome (CRS) was identified. Cohort studies with an unvaccinated comparison group were limited in number and size, and based on these only a theoretical additional risk of 6 or more cases of CRS per 1000 vaccinated women (0% observed, upper 95% CI 0.6%) could be excluded. Based on cohorts of vaccinated rubella susceptible pregnant women a maximum theoretical risk of 1 CRS case in 1008 vaccinated women (0% observed, upper 95% CI 0.099%) was estimated. Asymptomatic rubella vaccine virus infection of the neonate was also noted (fixed effects estimate of risk overall 1.74%, 95% CI 1.21, 2.28). CONCLUSION: There is no evidence that CRS is caused by rubella-containing vaccines but transplacental vaccine virus infection can occur. CRS is effectively prevented by vaccination, thus the risk/benefit balance is unequivocally in favour of vaccination. The data confirm previous recommendations that inadvertent vaccination during pregnancy is not an indication for termination of pregnancy.