Age-specific prevalence of IgG against measles/rubella and the impact of routine and supplementary immunization activities: A multistage random cluster sampling study with mathematical modelling.

BACKGROUND: Vietnam continues to have measles and rubella outbreaks following supplementary immunization activities (SIA) and routine immunization despite both having high reported coverage. To evaluate immunization activities, age-specific immunity against measles and rubella, and the number of averted Congenital Rubella Syndrome (CRS) cases, must be estimated. METHODS: Dried blood spots were collected from 2091 randomly selected individuals aged 1-39 years. Measles and rubella virus-specific immunoglobulin G (IgG) were measured by enzyme immunoassay. Results were considered positive at ≥120 mIU/mL for measles and ≥10 IU/mL for rubella. The number of CRS cases averted by immunization since 2014 were estimated using mathematical modelling. RESULTS: Overall IgG seroprevalence was 99.7% (95%CI: 99.2-99.9) for measles and 83.6% (95%CI: 79.3-87.1) for rubella. Rubella IgG seroprevalence was higher among age groups targeted in the SIA than in non-targeted young adults (95.4% [95%CI: 92.9-97.0] vs 72.4% [95%CI: 63.1-80.1]; P < 0.001). The estimated number of CRS cases averted in 2019 by immunization activities since 2014 ranged from 126 (95%CI: 0-460) to 883 (95%CI: 0-2271) depending on the assumed postvaccination reduction in the force of infection. CONCLUSIONS: The results suggest the SIA was effective, while young adults born before 1998 who remain unprotected for rubella require further vaccination.

High rate of rubella seronegativity in perinatally-infected HIV women of childbearing age: A case-control study.

Rubella infection is a vaccine preventable disease. Maternal infection during pregnancy may lead to congenital infection and severe foetal malformations. Thanks to antiretroviral therapy, perinatally HIV-infected women have better prognosis and are now experiencing pregnancy. We evaluated the rate of rubella seronegativity in a cohort of HIV perinatally-infected women of childbearing age. A high rate of seronegativity was found in this group as compared to age-matched non-perinatally infected HIV-infected women (34.5% vs 6.90%, p < 0.01). MMR administration before rubella testing was identified in 75.8% of perinatally-infected women (22/29) with a mean of 2 doses (range: 1-3 doses). HIV perinatally-infected women of childbearing age should be screened repeatedly for rubella immunity.

Modelling a Supplementary Vaccination Program of Rubella Using the 2012⁻2013 Epidemic Data in Japan.

From 2012-2013, Japan experienced a major epidemic of rubella, involving a total of 12,614 rubella cases and 45 confirmed cases of congenital rubella syndrome (CRS). One of the contributory factors in this outbreak may have been that the majority of adult males remained unvaccinated. To plan for a supplementary immunization program (SIP) to elevate the herd immunity level, it is critical to determine the required amount of vaccine and identify the target age groups among males for the SIP. The present study aimed to answer these policy questions, employing a mathematical model and analyzing epidemiological datasets from 2012-2013. Our model allowed us to reconstruct the age- and sex-dependent transmission patterns, and the effective reproduction number during the exponential growth phase in 2013 was estimated to be 1.5. The computed next-generation matrix indicated that vaccinating adult males aged from 20-49 years in 2013, using at least 17 million doses, was considered essential to prevent a major epidemic in the future. The proposed model also indicated that, even with smaller doses of vaccine, the SIP in adult males could lead to a substantial reduction in the incidence of rubella, as well as CRS. Importantly, the present study endorses a substantial background risk of observing another major epidemic from 2018-2019, in which cases may be dominated by adult males aged from 25-54 years, that is, our identified age groups plus a five-year time lag from 2013 to 2018.

Seroprevalencia de anticuerpos IgG antirubéola y anticitomegalovirus en mujeres entre 16 y 40 años residentes en Tunja, Colombia / Seroprevalence of anti-rubella and anti-cytomegalovirus IgG antibodies in women aged between 16 and 40 years, living in Tunja, Colombia

RESUMEN Objetivo Determinar la seroprevalencia de anticuerpos IgG anti-rubéola y anti-citomegalovirus en un grupo de mujeres entre 16 y 40 años, residentes en Tunja. Métodos Investigación descriptiva de corte transversal, en la cual se incluyeron mujeres de 16 a 40 años, por medio de un muestreo no probabilístico por conveniencia. Las variables sociodemográficas fueron registradas mediante encuesta. Se empleó ensayo inmunoenzimático para la determinación cuantitativa de anticuerpos IgG frente a rubéola y citomegalovirus en suero. La estadística aplicada al estudio se llevó a cabo por medio del programa estadístico SPSS versión 21. Resultados El estudio incluyó un total de 154 mujeres en edad fértil, estableciéndose una seropositividad para IgG anti-rubéola de 96,1% (n=148) (IC 95% 93,0 - 99,1) y anti-citomegalovirus de 90,9% (n=140) (IC 95% 86,3 - 95,4). Conclusión Una de cada diez mujeres en estudio está en riesgo de adquirir una infección primaria por citomegalovirus y una de cada 30 por rubéola. El control prenatal por medio de determinaciones serológicas frente a citomegalovirus y rubéola durante el embarazo es primordial en estos casos.(AU)

ABSTRACT Objective To determine the seroprevalence of anti-rubella and anti-cytomegalovirus IgG antibodies in a group of women aged between 16 and 40 years, residents of Tunja. Methods Descriptive, cross-sectional research in women aged between 16 and 40 years included by means of non- probability sampling for convenience. Sociodemographic variables were recorded by applying a survey. An enzyme immunoassay was used for the quantitative determination of rubella and cytomegalovirus IgG antibodies in serum. The statistical analysis was carried out using the statistical program SPSS version 21. Results The study included 154 women of childbearing age, establishing seropositivity for anti-rubella IgG of 96.1% (n=148) (95%CI: 86.3 - 95.4) Conclusion One in ten women included in the study is at risk of primary cytomegalo-virus infection and one in 30 of rubella infection. Prenatal care using serological determinations of cytomegalovirus and rubella during pregnancy is essential in these cases.(AU)

Rubella immune status of neonates - a window towards seroprevalence among childbearing women.

BACKGROUND: When contracted in pregnancy, rubella may cause serious chronic infection of the fetus and development of Congenital Rubella Syndrome. Despite widespread application of rubella vaccination, periodical outbreaks are still being reported worldwide. The aim of this study was to determine rubella seroprevalence and antibody levels in neonates in Serbia as a proxy of maternal serostatus. METHODS: ELISA based serological testing for rubella was done in 599 neonates treated at the Institute of Neonatology in Belgrade, from January 2010 to December 2011. All individuals with rubella IgG concentration ≥10 IU/ml were considered seropositive for rubella. RESULTS: The mean age of enrolled neonates was 18 ± 6 days. The overall seroprevalence of rubella IgG antibodies among the tested neonates was 540/599(90.2 %, 95 % CI: 87.5-92.3). Seropositivity rate among sera of the neonates enrolled in 2010 was significantly higher than those collected in 2011 (p < 0.0001). There was no difference in average maternal age, gestational age or frequency of receiving blood products among the two study years. Significant high seropositivity rate was observed among neonates from mother aged >30 as compared to those from mothers aged <20 years (p = 0.02). Significant difference was also found between average IgG titers in the two study years (79 IU/mL in 2010 vs. 46 IU/mL in 2011, p < 0.0001). CONCLUSION: We report on high rubella seroprevalence among newborns in Serbia, as a proxy of rubella serostatus of childbearing aged women. Notably, declining trend of rubella antibodies toward diminishing titers suggest the importance of sustained rubella serosurvey and antenatal screening at the national level.

Immunolocalization and Distribution of Rubella Antigen in Fatal Congenital Rubella Syndrome.

BACKGROUND: An estimated 100,000 cases of congenital rubella syndrome (CRS) occur worldwide each year. The reported mortality rate for infants with CRS is up to 33%. The cellular mechanisms responsible for the multiple congenital defects in CRS are presently unknown. Here we identify cell types positive for rubella virus (RV) in CRS infants. METHODS: Cells and organs involved in RV replication were identified in paraffin-embedded autopsy tissues from three fatal case-patients by histopathologic examination and immunohistochemical (IHC) staining using a rabbit polyclonal RV antibody. Normal rabbit antisera and RV antisera preabsorbed with highly purified RV served as negative controls. RESULTS: RV antigen was found in interstitial fibroblasts in the heart, adventitial fibroblasts of large blood vessels, alveolar macrophages, progenitor cells of the outer granular layer of the brain, and in capillary endothelium and basal plate in the placenta. The antibody specificity was verified by IHC staining of multiple tissue sections from other infectious disease cases. RV infection of each cell type is consistent with abnormalities which have been identified in patients with CRS, in the heart, large blood vessels, and brain. Antigen distribution was consistent with inflammatory response to vascular injury and systemic spread of RV. CONCLUSIONS: The identification of RV positive cell types in CRS is important to better understand the pathology and pathogenesis of CRS.

Immunity to polio, measles and rubella in women of child-bearing age and estimated congenital rubella syndrome incidence, Cambodia, 2012.

Significant gaps in immunity to polio, measles, and rubella may exist in adults in Cambodia and threaten vaccine-preventable disease (VPD) elimination and control goals, despite high childhood vaccination coverage. We conducted a nationwide serological survey during November-December 2012 of 2154 women aged 15-39 years to assess immunity to polio, measles, and rubella and to estimate congenital rubella syndrome (CRS) incidence. Measles and rubella antibodies were detected by IgG ELISA and polio antibodies by microneutralization testing. Age-structured catalytic models were fitted to rubella serological data to predict CRS cases. Overall, 29.8% of women lacked immunity to at least one poliovirus (PV); seroprevalence to PV1, PV2 and PV3 was 85.9%, 93.4% and 83.3%, respectively. Rubella and measles antibody seroprevalence was 73.3% and 95.9%, respectively. In the 15-19 years age group, 48.2% [95% confidence interval (CI) 42.4-54.1] were susceptible to either PV1 or PV3, and 40.3% (95% CI 33.0-47.5) to rubella virus. Based on rubella antibody seroprevalence, we estimate that >600 infants are born with CRS in Cambodia annually. Significant numbers of Cambodian women are still susceptible to polio and rubella, especially those aged 15-19 years, emphasizing the need to include adults in VPD surveillance and a potential role for vaccination strategies targeted at adults.

Identification of germinal centres in the lymph node of a patient with hyperimmunoglobulin M syndrome associated with congenital rubella.

BACKGROUND: The hyper immunoglobulin M syndrome (HIM) associated with congenital rubella infection (rHIM) is an extremely rare disorder, where patients have elevated serum IgM in association with reduced IgG and IgA. We have previously shown that in contrast to X-linked HIM (XHIM), a patient with well-characterised rHIM is able to express functional CD40 ligand, undergo immunoglobulin isotype switching and to generate memory B cells. Here we describe the ultrastructural features of an excised lymph node from this patient. METHODS: An inguinal lymph node was surgically removed and examined histologically as well as by immunohistochemistry. It was then stained with multiple fluorescent dyes to visualize the cellular interactions within the node. Flow cytometry was undertaken on a cellular suspension from the node. FINDINGS: Our patient has normal lymph node architecture by light microscopy. Immunohistochemistry studies showed the presence of scattered germinal centres. Polychromatic immunofluorescence staining showed disruption of the architecture with mostly abnormal germinal centres. A small number of relatively intact germinal centres were identified. Both IgM and IgG bearing cells were identified in germinal centres. INTERPRETATION: In contrast to XHIM where germinal centres are absent, the presence of small numbers of relatively normal germinal centres explain our previous identification of isotype switched memory B cells in rHIM.

Congenital rubella syndrome and immunity status of immigrant women living in southern Italy: a cross-sectional, seroepidemiological investigation.

OBJECTIVES: A National Programme to eliminate Measles and Congenital Rubella was implemented in Italy in 2003. It aimed to achieve elimination by 2010 in line with the targets set by the World Health Organization (WHO) European Region. The aim of this study was to determine the prevalence of rubella antibodies in samples of immigrant women living in southern Italy. METHOD: A seroepidemiologic study was conducted from 1 January 2008 to June 30 2009. 489 immigrant women resident in Messina were enrolled in the study. The detection of rubella antibodies was performed using a microparticle enzyme immunoassay. A questionnaire was used to collect demographic data including age, country of origin, educational level and knowledge about rubella. RESULTS: The results of the seroepidemiological survey to detect rubella antibodies showed an overall seropositivity rate of 82.2%. Generally, knowledge about rubella and congenital rubella syndrome was lacking. CONCLUSION: Many immigrants are susceptible to rubella and may benefit from vaccination programmes. Additional catch-up vaccination strategies are urgently needed to eliminate the risk of congenital rubella syndrome for future generations.

Congenital rubella syndrome in child of woman without known risk factors, New Jersey, USA.

We report a case of congenital rubella syndrome in a child born to a vaccinated New Jersey woman who had not traveled internationally. Although rubella and congenital rubella syndrome have been eliminated from the United States, clinicians should remain vigilant and immediately notify public health authorities when either is suspected.

[Update for the standard procedures of diagnosis and therapy in cases of congenital rubella]. / Aggiornamento delle procedure operative standard per la diagnosi e la cura dei casi di rosolia congenita.

Congenital Rubella is the dramatic consequence of rubella during gestation. A combined strategy of Measles and Rubella universal vaccination on children and selective vaccination of susceptible women has been shown effective in the elimination of congenital rubella requiring an incidence of < 1 case of CRS per 100,000 live births. Verification processes of rubella elimination require that physicians early and appropriately diagnose all cases of congenital rubella, including those unpatent at birth. The paper highlights clinical and laboratory aspects channeling diagnosis of congenital rubella infection or syndrome even after the first year of life, and the short- and long-term management criteria.

Health economics of rubella: a systematic review to assess the value of rubella vaccination.

BACKGROUND: Most cases of rubella and congenital rubella syndrome (CRS) occur in low- and middle-income countries. The World Health Organization (WHO) has recently recommended that countries accelerate the uptake of rubella vaccination and the GAVI Alliance is now supporting large scale measles-rubella vaccination campaigns. We performed a review of health economic evaluations of rubella and CRS to identify gaps in the evidence base and suggest possible areas of future research to support the planned global expansion of rubella vaccination and efforts towards potential rubella elimination and eradication. METHODS: We performed a systematic search of on-line databases and identified articles published between 1970 and 2012 on costs of rubella and CRS treatment and the costs, cost-effectiveness or cost-benefit of rubella vaccination. We reviewed the studies and categorized them by the income level of the countries in which they were performed, study design, and research question answered. We analyzed their methodology, data sources, and other details. We used these data to identify gaps in the evidence and to suggest possible future areas of scientific study. RESULTS: We identified 27 studies: 11 cost analyses, 11 cost-benefit analyses, 4 cost-effectiveness analyses, and 1 cost-utility analysis. Of these, 20 studies were conducted in high-income countries, 5 in upper-middle income countries and two in lower-middle income countries. We did not find any studies conducted in low-income countries. CRS was estimated to cost (in 2012 US$) between $4,200 and $57,000 per case annually in middle-income countries and up to $140,000 over a lifetime in high-income countries. Rubella vaccination programs, including the vaccination of health workers, children, and women had favorable cost-effectiveness, cost-utility, or cost-benefit ratios in high- and middle-income countries. CONCLUSIONS: Treatment of CRS is costly and rubella vaccination programs are highly cost-effective. However, in order for research to support the global expansion of rubella vaccination and the drive towards rubella elimination and eradication, additional studies are required in low-income countries, to tackle methodological limitations, and to determine the most cost-effective programmatic strategies for increased rubella vaccine coverage.

Models of strategies for control of rubella and congenital rubella syndrome-a 40 year experience from Australia.

We investigated the impact of vaccination on rubella epidemiology in Australia, using a mathematical model fitted to Australian serosurvey data and incorporating pre-vaccination European estimates of rubella transmissibility. Mass infant measles-mumps-rubella (MMR) vaccination produced a 99% reduction in both rubella and congenital rubella syndrome (CRS) incidence by 2010 compared to the pre-vaccination era (1960-70). The model is consistent with reductions in CRS based on surveillance of congenital hearing impairment. Model simulations suggest that selective schoolgirl vaccination (1971-88) was associated with a 90% reduction in CRS incidence, but only a 1-4% reduction in rubella incidence. Our model predicted that these reductions in rubella were much less vulnerable to reductions in MMR vaccine coverage than for measles. In the future, a less than 15% decrease in MMR vaccine coverage is estimated to have minimal impact before 2060, but a 20% reduction may result in a 7-fold increase in rubella incidence, with the effective reproductive number R rising from 0.28 to 0.78 by 2060. The 99% reduction in both rubella and CRS incidence and low effective reproductive number (R≤0.28) we documented after 2010 are consistent with Australia having achieved rubella elimination.

Rubella vaccine: new horizon in prevention of congenital rubella syndrome in the India.

Rubella is a contagious viral disease, which mainly affects the fetus, if the mother is infected in the 1st trimester of her pregnancy. All adolescent girls (aged 11 to 19 y) and women of childbearing age are at risk of developing rubella. This disease is mild and self-limiting, and incubation period is 2-3 weeks. Humans are the only hosts for rubella. Rubella infection during pregnancy may lead to abortions, stillbirth or congenital deformities (birth defects). Moreover it is surprising to know that over 200,000 babies are born with birth defects because of Rubella infection during pregnancy in the Indian sub-continent. The risk of fetal infection is highest in first trimester; the infection rate declines between 12-28 weeks, suggesting that the placenta may prevent transfer of virus but not completely. The incidence of defects is inversely related to the time of maternal infection. Rubella outbreaks have been reported from many countries in South East Asian region with congenital rubella syndrome (CRS) due to maternal rubella being on the increase in many countries. In India, although the endemicity of rubella is established, the majority of cases remain undiagnosed, being subclinical or clinically mild. Consequently, in spite of evidence of CRS in all States of India, no distinct policy has been envisaged for assessing the burden of rubella, and no control measures against this silent crippling disease are in place. The European Regional Committee of the World Health Organization has adopted the goals of "Elimination of CRS" in the Health for All programs. There is no treatment for rubella. Vaccination is the only way to prevent all these complications.

Rubella seroepidemiology and estimations of the catch-up immunisation rate and persistence of antibody titers in pregnant women in Taiwan.

OBJECTIVE: To examine rubella seroepidemiology, and estimate rates of catch-up immunisation and persistence of antibody titers in pregnant women in Taiwan after mass immunisation. DESIGN: A retrospective study. SETTING: Two medical centres and four regional hospitals specialising in obstetric care. SAMPLE: A total of 43,640 prenatal rubella test results for pregnant women from 2001 to 2008. METHODS: Rubella immunoglobulin G (IgG) antibody assay. MAIN OUTCOME MEASURES: Seronegativity, rate of catch-up immunization, and antibody decline. RESULTS: The seronegativity was 10.9% in all pregnant women. Immigrant women had higher seronegativity than indigenous women (OR 2.86; 95% CI 2.65, 3.01). Indigenous women born prior to implementation of the vaccination programmes were more susceptible (20.1%) to rubella infection than were women born thereafter (6.7%). Rates of seropositive conversion were low in both Taiwanese-born and foreign-born women (11.5 and 30.7%, respectively). The rubella antibody titers for vaccinated Taiwanese women in the 1971-1976 and after-1976 birth cohorts declined by 0.6 and 2.3% per year, respectively. CONCLUSIONS: This study demonstrates high seronegativity of older indigenous and immigrant women, a low catch-up immunisation rate, and the persistence of rubella antibodies in Taiwan after mass vaccination. Our study suggests that a single dose of rubella vaccine in teenagers effectively increased rubella seropositivity during their childbearing years. This finding is useful for countries that lack the resources necessary for a two-dose regimen. We recommend free rubella antibody tests to women of childbearing age and free vaccination as required. All postpartum women testing negative for rubella antibodies should be vaccinated before they leave hospital.