Rubella Elimination Research Articles

Is it time to reconsider measles, mumps, and rubella immunisation strategies?

Since the late 1990s, measles has continued to be a public health problem, and so WHO launched a global plan for measles and congenital rubella elimination in 1997. Despite the relevant efforts, the goals of elimination have not yet been achieved, and the deadline to reach them has been postponed many times. Moreover, even in areas where high immunisation coverage has been registered, epidemics of measles have occurred in the past 10 years worldwide.1–4 What can be done to eliminate this disease?

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.

Progress Toward Rubella Elimination - Western Pacific Region, 2000-2019.

Rubella is the leading vaccine-preventable cause of birth defects. Rubella typically manifests as a mild febrile rash illness; however, infection during pregnancy, particularly during the first trimester, can result in miscarriage, fetal death, or a constellation of malformations known as congenital rubella syndrome (CRS), commonly including one or more visual, auditory, or cardiac defects (1). In 2012, the Regional Committee of the World Health Organization (WHO) Western Pacific Region (WPR)* committed to accelerate rubella control, and in 2017, resolved that all countries or areas (countries) in WPR should aim for rubella elimination† as soon as possible (2,3). WPR countries are capitalizing on measles elimination activities, using a combined measles and rubella vaccine, case-based surveillance for febrile rash illness, and integrated diagnostic testing for measles and rubella. This report summarizes progress toward rubella elimination and CRS prevention in WPR during 2000-2019. Coverage with a first dose of rubella-containing vaccine (RCV1) increased from 11% in 2000 to 96% in 2019. During 1970-2019, approximately 84 million persons were vaccinated through 62 supplementary immunization activities (SIAs) conducted in 27 countries. Reported rubella incidence increased from 35.5 to 71.3 cases per million population among reporting countries during 2000-2008, decreased to 2.1 in 2017, and then increased to 18.4 in 2019 as a result of outbreaks in China and Japan. Strong sustainable immunization programs, closing of existing immunity gaps, and maintenance of high-quality surveillance to respond rapidly to and contain outbreaks are needed in every WPR country to achieve rubella elimination in the region.

The Burden of Disease from Congenital Rubella Syndrome in Lesotho

Background: Congenital rubella syndrome (CRS) causes severe birth defects and is preventable. In line with the global vision for measles and rubella elimination, Lesotho introduced the measles-rubella (MR) vaccine into the routine immunization schedule in February 2017. The aim of the study was to show the burden of CRS in Lesotho before the introduction of the rubella vaccine. Methods: This was a cross-sectional descriptive study. Data was extracted from several sources at Queen Mamohato Memorial Hospital including inpatient, outpatient, electronic and laboratory records as well as expert interviews. Files of infants less than 12 months with CRS during the period January 2012 to December 2016 were selected. Results: There were five laboratory and 4 clinically confirmed CRS cases. One case also had Cytomegalovirus (CMV) co-infection. Mohales’ Hoek district had the highest number of cases (33.3%). Six of the districts had at least one case of CRS within the study period. There were no cases in 4 districts. Most (56%) of the CRS cases were reported in 2015. We were unable to determine the incidence of CRS in Lesotho in this study. Conclusion: The detection of 9 CRS cases in Lesotho over the period under review is of high public health importance.There is an immunity gap among mothers of child bearing age which shows an opportunity for future immunization. Prospective CRS case-based surveillance would be useful in determining accurate estimates of the burden of CRS and the impact of the introduction of rubella-containing vaccine into the routine immunization schedule.

ANALISI FAKTOR YANG BERHUBUNGAN DENGAN PENERIMAAN IBU TERHADAP IMUNISASI MR PADA MURID SEKOLAH DASAR

The promotion of Measles Rubella immunization campaign is a government strategy to achieve elimination of measles and rubella by 2020. This immunization is targeting all Indonesian children between the ages of nine months and 15 years and will aim to reach 95% immunization coverage. Not all parents receive the MR immunization program. Air Merah Village is one of the villages that reject high immunization. This study is aimed to analyze the factors associated with mother’s acception of measles rubella immunization at primary school children of 112245 primary school at Air Merah Village, Kampung Rakyat Sub-district, South Labuhanbatu Districts. This study is a quantitative study with descriptive analytics method. This study uses Consecutive sampling techniques and the data are collected using questionnare with interview method. Data analysis procedure of this study used univariat, bivariat and multivariat with chi-square test. The result shows that 73,3% respondents did not received measles rubella immunization. The result of chi-square test show that variabel education level, job status, knowledge about measles rubella immunization, perceived susceptibility, perceived severity, perceived benefit, perceived barriers, and family supports are significantly associated with the acceptance of measles rubella immunization (p-value < 0,05). While age variableare not significantly associated with acceptance of measles rubella immunization (v-value > 0,05). Sugestion from this study, it needs to give more education about the importance of measles rubella immunization from related parties to the parents, especially for mother, to improve their awareness to join measles immunization

Strategies for elimination of rubella in pregnancy and of congenital rubella syndrome in high and upper-middle income countries.

SummaryRubella infection generally leads to mild symptoms; otherwise, in pregnant women it can cause severe damages. The only way to prevent rubella is vaccine. Before the introduction of the vaccine, up to 4 babies in 1000 live births were born with CRS.This work aims to review the most important strategies for the elimination of CRS in upper and high-income countries.Papers were selected through a PubMed search up to January 2019, using keywords rubella, congenital rubella syndrome and epidemiology. Articles published in the last 12 years and referred to upper income and high-income countries in title or abstract were included.Sixty-five papers were selected dealing with one or more of the following strategies: increasing of rubella vaccination coverage in childbearing age women, males, immigrants; exploitation of all appropriate occasions; improving of rubella surveillance.Despite numerous suggestions and indications for valid strategies to eliminate rubella in pregnancy and congenital rubella syndrome, a practical application is often missing.

Rubella infection: Advances and challenges in the diagnosis and prevention of Congenital Rubella Syndrome

Rubella remains an important pathogen worldwide, with many cases of congenital rubella syndrome per year. Rubella vaccination is included in the vaccination program of many countries. WHO has set goals for the elimination of measles and rubella and prevention of congenital rubella syndrome by 2020. Worldwide, the rubella vaccine is highly effective and safe, and as a result, endemic rubella transmission has been halted in the Americas since 2009. Incomplete rubella vaccination programs result in continuous disease transmission, as evidenced by major recent outbreaks in some countries around the world. In this review, we present the rubella control, elimination and eradication policies and a brief review of the rubella laboratory diagnosis.

Measles and rubella microarray array patches to increase vaccination coverage and achieve measles and rubella elimination in Africa.

The African Region is committed to measles elimination by 2020 but coverage with the first dose of measles-containing vaccine was only 70% in 2017. Several obstacles to achieving high coverage with measles and rubella vaccines exist, some of which could be overcome with new vaccine delivery technologies. Microarray array patches (MAPs) are single-dose devices used for transcutaneous administration of molecules, including inactivated or attenuated vaccines, that penetrate the outer stratum corneum of the skin, delivering antigens to the epidermis or dermis. MAPs to deliver measles and rubella vaccines have the potential to be a transformative technology to achieve elimination goals in the African Region. MAPs for measles and rubella vaccination have been shown to be safe, immunogenic and thermostable in preclinical studies but results of clinical studies in humans have not yet been published. This review summarizes the current state of knowledge of measles and rubella MAPs, their potential advantages for immunization programs in the African Region, and some of the challenges that must be overcome before measles and rubella MAPs are available for widespread use.

Comparison of virological and serological methods for laboratory confirmation of rubella

BackgroundWork toward rubella elimination has accelerated globally. A reliable laboratory confirmation of rubella-suspected cases is required for effective surveillance in the rubella-elimination phase. The use of adequate specimens is a key to improving the quality of this surveillance. Study designWe conducted rubella virus (RUBV) isolation and RUBV genome or anti-RUBV IgM detection on 1023 specimens from 372 rubella- or measles-suspected cases collected through the national surveillance program in Sakai city of Osaka prefecture, Japan between 2011 and 2013. The resulting data were analyzed by specimen type, collection date, and immunological status. ResultsAmong the three specimen types (throat swab, serum or plasma, and urine) collected through 10 days post-rash onset, the highest success rates for RUBV genome detection and RUBV isolation were obtained using throat swabs. In agreement with previous work, RUBV-specific IgM were undetectable in 50% of the rubella-confirmed cases until 3 days after rash onset. The success rates of RUBV genome detection and RUBV isolation declined in association with the appearance of RUBV-specific antibodies in blood, especially in serum, plasma, or urine samples. ConclusionThroat swabs are the most optimal specimen types for both RUBV genome detection and RUBV isolation; serum/plasma samples may be suboptimal, especially for RUBV isolation. The findings from this study will provide useful information for improving laboratory surveillance for rubella in the elimination phase.

Towards elimination of measles and rubella in Italy: Progress and challenges

IntroductionIn the WHO European Region, endemic transmission of measles and rubella had been interrupted by 37 and 42 of the 53 member states (MSs), respectively, by 2018. Sixteen MSs are still endemic for measles, 11 for rubella and nine for both diseases, the latter including Italy. Elimination is documented by each country’s National Verification Committee (NVC) through an annual status update (ASU).ObjectiveBy analysing data used to produce the ASUs, we aimed to describe the advances made by Italy towards elimination of measles and rubella. Moreover, we propose a set of major interventions that could facilitate the elimination process.MethodsA total of 28 indicators were identified within the six core sections of the ASU form and these were evaluated for the period 2013–2018. These indicators relate to the incidence of measles/rubella; epidemiological investigation of cases; investigation of outbreaks; performance of the surveillance system; population immunity levels; and implementation of supplemental immunization activities (SIAs).ResultsFrom 2013 to 2018, epidemiological and laboratory analyses of measles cases in Italy improved substantially, allowing timely investigation in 2017 and 2018 of most outbreak and sporadic cases and identification of the majority of genotypic variants. Moreover, since 2017, vaccination coverage has increased significantly. Despite these improvements, several areas of concern emerged, prompting the following recommendations: i) improve outbreak monitoring; ii) strengthen the MoRoNet network; iii) increase the number of SIAs; iv) reinforce vaccination services; v) maintain regional monitoring; vi) design effective communication strategies; vii) foster the role of general practitioners and family paediatricians.ConclusionsThe review of national ASUs is a crucial step to provide the NVC with useful insights into the elimination process and to guide the development of targeted interventions. Against this background, the seven recommendations proposed by the NVC have been shared with the Italian Ministry of Health and the Technical Advisory Group on measles and rubella elimination and have been incorporated into the new Italian Elimination Plan 2019–2023 as a technical aid to facilitate the achievement of disease elimination goals.

Elimination of congenital rubella: a seroprevalence study of pregnant women and women of childbearing age in Italy

ABSTRACT Prevention of congenital rubella is achieved by vaccination of susceptible women of childbearing age. In Italy, the National Plan for Measles and Congenital Rubella Elimination 2010–2015 implemented catch-up vaccination activities targeting susceptible adolescents and young adults, including women of childbearing age. The aim of this study was to assess the immunity against rubella in women of childbearing age in Tuscany (Central Italy) and Apulia (Southern Italy) and pregnant women in Apulia after the implementation of the National Plan for Measles and Congenital Rubella Elimination. Overall, anti-rubella IgG prevalence in women of childbearing age samples was 88.6% in Tuscany and 84.3% in Apulia. The lowest prevalence was observed in samples of 26–35 years old women of childbearing age in Apulia with 77.8%. Only 62.7% of samples from 26–35 years old pregnant women had IgG against rubella, and one sample out of 95 was positive to IgM. The findings of this study highlight the need for increasing awareness on the risk of contracting rubella infection during pregnancy and implement vaccination strategies to create opportunities for administration of rubella containing vaccines in young girls and women of childbearing age.

Genetic diversity of rubella virus at the present stage of rubella elimination and congenital rubella prevention programs

The review is devoted to an analysis of the genetic diversity of the rubella virus. Historical and geographical data of the circulation of various genotypes of the rubella virus were presented. The tendency to reduce the genetic diversity of the virus in the world as a result of the rubella elimination programs have been shown.

Descriptive epidemiology of rubella disease and associated virus strains in Uganda.

Rubella virus causes a mild disease; however, infection during the first trimester of pregnancy may lead to congenital rubella syndrome (CRS) in over 80% of affected pregnancies. Vaccination is recommended and has been shown to effectively reduce CRS incidence. Uganda plans to introduce routine rubella vaccination in 2019. The World Health Organization recommends assessing the disease burden and obtaining the baseline molecular virological data before vaccine introduction. Sera collected during case‐based measles surveillance from January 2005 to July 2018 were tested for rubella immunoglobulin M (IgM) antibodies. Sera from confirmed rubella outbreaks from January 2012 to August 2017 were screened using real‐time reverse‐transcription polymerase chain reaction (RT‐PCR); for positive samples, a region within the E1 glycoprotein coding region was amplified and sequenced. Of the 23 196 suspected measles cases serologically tested in parallel for measles and rubella, 5334 (23%) were rubella IgM‐positive of which 2710 (50.8%) cases were females with 2609 (96.3%) below 15 years of age. Rubella IgM‐positive cases were distributed throughout the country and the highest number was detected in April, August, and November. Eighteen (18%) of the 100 sera screened were real‐time RT‐PCR‐positive of which eight (44.4%) were successfully sequenced and genotypes 1G and 2B were identified. This study reports on the seroprevalence and molecular epidemiology of rubella. Increased knowledge of former and current rubella viruses circulating in Uganda will enhance efforts to monitor the impact of vaccination as Uganda moves toward control and elimination of rubella and CRS.

Progress Toward Rubella and Congenital Rubella Syndrome Control and Elimination - Worldwide, 2000-2018.

Rubella is a leading cause of vaccine-preventable birth defects. Although rubella virus infection usually causes a mild febrile rash illness in children and adults, infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, stillbirth, or a constellation of birth defects known as congenital rubella syndrome (CRS). A single dose of rubella-containing vaccine (RCV) can provide lifelong protection (1). In 2011, the World Health Organization (WHO) updated guidance on the use of RCV and recommended capitalizing on the accelerated measles elimination activities as an opportunity to introduce RCV (1). The Global Vaccine Action Plan 2011-2020 (GVAP) includes a target to achieve elimination of rubella in at least five of the six WHO regions by 2020 (2). This report on the progress toward rubella and CRS control and elimination updates the 2017 report (3), summarizing global progress toward the control and elimination of rubella and CRS from 2000 (the initiation of accelerated measles control activities) and 2012 (the initiation of accelerated rubella control activities) to 2018 (the most recent data) using WHO immunization and surveillance data. Among WHO Member States,* the number with RCV in their immunization schedules has increased from 99 (52% of 191) in 2000 to 168 (87% of 194) in 2018†; 69% of the world's infants were vaccinated against rubella in 2018. Rubella elimination has been verified in 81 (42%) countries. To make further progress to control and eliminate rubella, and to reduce the equity gap, introduction of RCV in all countries is important. Likewise, countries that have introduced RCV can achieve and maintain elimination with high vaccination coverage and surveillance for rubella and CRS. The two WHO regions that have not established an elimination goal (African [AFR] and Eastern Mediterranean [EMR]) should consider establishing a goal.§.

Caracterización de los resultados correspondientes al brote de sarampión de Madrid de 2019 en las muestras clínicas procesadas en el Laboratorio Regional de Salud Pública

En la primavera de 2019 se ha producido en la Comunidad de Madrid un aumento de casos de sarampión. El objetivo de este estudio es describir el tipo de muestras clínicas estudiadas y los resultados obtenidos en este brote. Entre el 1 de abril y el 25 de junio de 2019 se procesaron 193 muestras biológicas correspondientes a 109 sospechas clínicas de sarampión. Las determinaciones serológicas (IgM e IgG frente a sarampión y rubéola) se llevaron a cabo por ELISA indirecto. La amplificación de ácidos nucleicos de los virus del sarampión y la rubéola se efectuó mediante RT-PCR. Se confirmaron 44 casos de sarampión. Dos de ellos habían sido vacunados muy recientemente y ambos presentaban el genotipo vacunal A. Los amplificados de todas las cepas salvajes (21) eran D8. En esta serie, el tiempo medio observado entre recepción de muestras y obtención del resultado positivo fue de 0,5 días. En 32 casos confirmados se dispuso de muestras tanto de exudado faríngeo para RT-PCR como de sangre para serología y en 32 la RT-PCR resultó positiva (sensibilidad 100%, IC95% 86,7- 99,7) mientras que en 22 la IgM fue positiva (sensibilidad 68,8%, IC95% 49,9- 83,3). Inversamente, en 49 sospechas descartadas se dispuso de muestras de exudado faríngeo para RT-PCR como de sangre para serología y en 49 la RT-PCR resultó negativa (especificidad 100%, IC95% 90,9- 99,8). En 1 muestra de una sospecha descartada la IgM fue positiva (especificidad 98,0%, IC95% 87,8- 99,9). En la etapa de eliminación del sarampión y la rubéola los estándares de vigilancia deben ir dirigidos a detectar todos los posibles casos. Para ello es preciso la obtención en tiempos correctos de las muestras biológicas adecuadas (suero y especialmente exudado faríngeo).

Algoritmo diagnóstico para la confirmación de casos de sarampión y rubéola en México.

Due to the successful implementation of measles and rubella elimination strategies, Mexico announced the interruption of endemic transmission of measles in 1996 and that of rubella in 2008. After a verification process, the region of the Americas was declared free of rubella and congenital rubella syndrome in 2015 and of measles in 2016. In order to maintain the elimination status in Mexico, it is essential to continue laboratory surveillance within the framework of the Global Measles and Rubella Laboratory Network. The Institute of Epidemiological Diagnosis and Reference, through the National Network of Public Health Laboratories, guarantees timely and reliable results in view of the possible reintroduction of these and other emerging pathogens.

Measles and rubella immunity in the population of Bhutan, 2017

BackgroundIn 2017, measles elimination was verified in Bhutan, and the country appears to have sufficiently high vaccination coverage to achieve rubella elimination. However, a measles and rubella serosurvey was conducted to find if any hidden immunity gaps existed that could threaten Bhutan’s elimination status. MethodsA nationwide, three-stage, cluster seroprevalence survey was conducted among individuals aged 1–4, 5–17, and >20 years in 2017. Demographic information and children’s vaccination history were collected, and a blood specimen was drawn. Serum was tested for measles and rubella immunoglobulin G (IgG). Frequencies, weighted proportions, and prevalence ratios for measles and rubella seropositivity were calculated by demographic and vaccination history, taking into account the study design. ResultsOf the 1325 individuals tested, 1045 (81%, 95% CI 78%–85%) were measles IgG seropositive, and 1290 (97%, 95% CI 95%–99%) were rubella IgG seropositive. Rubella IgG seropositivity was high in all three age strata, but only 47% of those aged 5–17 years were measles IgG seropositive. Additionally, only 41% of those aged 5–17 years who had documented receipt of two doses of measles– or measles-rubella–containing vaccine were seropositive for measles IgG, but almost all these children were rubella IgG seropositive. ConclusionsAn unexpected measles immunity gap was identified among children 5–17 years of age. It is unclear why this immunity gap exists; however, it could have led to a large outbreak and threatened sustaining of measles elimination in Bhutan. Based on this finding, a mass vaccination campaign was conducted to close the immunity gap.

Genetic Characterization of Measles and Rubella Viruses Detected Through Global Measles and Rubella Elimination Surveillance, 2016-2018.

All six World Health Organization (WHO) regions have established measles elimination goals, and three regions have a rubella elimination goal. Each region has established a regional verification commission to monitor progress toward measles elimination, rubella elimination, or both, and to provide verification of elimination* (1,2). To verify elimination, high-quality case-based surveillance is essential, including laboratory confirmation of suspected cases and genotyping of viruses from confirmed cases to track transmission pathways. In 2000, WHO established the Global Measles and Rubella Laboratory Network (GMRLN) to provide high-quality laboratory support for surveillance for measles, rubella, and congenital rubella syndrome (3). GMRLN is the largest globally coordinated laboratory network, with 704 laboratories supporting surveillance in 191 countries (4). This report updates a previous report and describes the genetic characterization of measles and rubella viruses during 2016-2018 (5). The genetic diversity of measles viruses (MeVs) and rubella viruses (RuVs) has decreased globally following implementation of measles and rubella elimination strategies. Among 10,857 MeV sequences reported to the global Measles Nucleotide Surveillance (MeaNS) database during 2016-2018, the number of MeV genotypes detected in ongoing transmission decreased from six in 2016 to four in 2018. Among the 1,296 RuV sequences submitted to the global Rubella Nucleotide Surveillance (RubeNS) database during the same period, the number of RuV genotypes detected decreased from five in 2016 to two in 2018. To strengthen laboratory surveillance for measles and rubella elimination, specimens should be collected from all confirmed cases for genotyping, and sequences from all wild-type measles and rubella viruses should be submitted to MeaNS and RubeNS in a timely manner.

Preclinical study of safety and immunogenicity of combined rubella and human papillomavirus vaccines: Towards enhancing vaccination uptake rates in developing countries

Rubella vaccine was not part of national immunization programs (NIP) in several countries in the Middle East and North Africa (MENA), South-East Asia (SEA), and South Africa regions until the year 2000. Therefore, immunization coverage of females older than 20 years old in these countries has been the focus of national campaigns for rubella elimination in developing countries. Vaccines against human papillomavirus (HPV) are not part of NIPs in developing countries. To enhance the advantages of rubella-directed immunization campaigns and to increase HPV vaccine uptake in developing countries, this study aimed to test the stability, potency, efficacy and safety of a combined rubella and HPV vaccine. Female BALB/c mice were immunized subcutaneously with proposed combined HPV16/HPV18 VLP and rubella vaccine at weeks (W) 0, 3 then with HPV vaccine at W 7. Immunized mice developed antigen-specific antibodies against rubella and HPV significantly higher than mice immunized with rubella or HPV vaccine alone. The combined vaccine induced significantly higher splenocyte proliferation than control groups. In addition, pro-inflammatory cytokines IL-4, IL-6, IL-2, and IFNγ levels were significantly higher in mice immunized with the combined vaccine than control groups. Overall, the combined vaccine was safe and immunogenic offering antibody protection as well as eliciting a cellular immune response against rubella and HPV viruses in a single vaccine. This combined vaccine can be of great value to females above 20 years old in the SEA, MENA and South Africa regions offering coverage to rubella vaccine and a potential increase in HPV vaccine uptake rates after appropriate clinical testing.

Accelerating measles and rubella elimination through research and innovation – Findings from the Measles & Rubella Initiative research prioritization process, 2016

The Measles & Rubella Initiative (M&RI) identified five key strategies to achieve measles and rubella elimination, including research and innovation to support cost-effective operations and improve vaccination and diagnostic tools. In 2016, the M&RI Research and Innovation Working Group (R&IWG) completed a research prioritization process to identify key research questions and update the global research agenda. The R&IWG reviewed meeting reports and strategic planning documents and solicited programmatic inputs from vaccination experts at the program operational level through a web survey, to identify previous research priorities and new research questions. The R&IWG then convened a meeting of experts to prioritize the identified research questions in four strategic areas: (1) epidemiology and economics, (2) surveillance and laboratory, (3) immunization strategies, and (4) demand creation and communications. The experts identified 19 priority research questions in the four strategic areas to address key areas of work necessary to further progress toward elimination. Future commitments from partners will be needed to develop a platform for improved coordination with adequate and predictable resources for research implementation and innovation to address these identified priorities.