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"Reef, Susan E."
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Using Seroprevalence and Immunisation Coverage Data to Estimate the Global Burden of Congenital Rubella Syndrome, 1996-2010: A Systematic Review
2016
The burden of Congenital Rubella Syndrome (CRS) is typically underestimated in routine surveillance. Updated estimates are needed following the recent WHO position paper on rubella and recent GAVI initiatives, funding rubella vaccination in eligible countries. Previous estimates considered the year 1996 and only 78 (developing) countries.
We reviewed the literature to identify rubella seroprevalence studies conducted before countries introduced rubella-containing vaccination (RCV). These data and the estimated vaccination coverage in the routine schedule and mass campaigns were incorporated in mathematical models to estimate the CRS incidence in 1996 and 2000-2010 for each country, region and globally.
The estimated CRS decreased in the three regions (Americas, Europe and Eastern Mediterranean) which had introduced widespread RCV by 2010, reaching <2 per 100,000 live births (the Americas and Europe) and 25 (95% CI 4-61) per 100,000 live births (the Eastern Mediterranean). The estimated incidence in 2010 ranged from 90 (95% CI: 46-195) in the Western Pacific, excluding China, to 116 (95% CI: 56-235) and 121 (95% CI: 31-238) per 100,000 live births in Africa and SE Asia respectively. Highest numbers of cases were predicted in Africa (39,000, 95% CI: 18,000-80,000) and SE Asia (49,000, 95% CI: 11,000-97,000). In 2010, 105,000 (95% CI: 54,000-158,000) CRS cases were estimated globally, compared to 119,000 (95% CI: 72,000-169,000) in 1996.
Whilst falling dramatically in the Americas, Europe and the Eastern Mediterranean after vaccination, the estimated CRS incidence remains high elsewhere. Well-conducted seroprevalence studies can help to improve the reliability of these estimates and monitor the impact of rubella vaccination.
Journal Article
Combining serological and contact data to derive target immunity levels for achieving and maintaining measles elimination
2019
Background
Vaccination has reduced the global incidence of measles to the lowest rates in history. However, local interruption of measles virus transmission requires sustained high levels of population immunity that can be challenging to achieve and maintain. The herd immunity threshold for measles is typically stipulated at 90–95%. This figure does not easily translate into age-specific immunity levels required to interrupt transmission. Previous estimates of such levels were based on speculative contact patterns based on historical data from high-income countries. The aim of this study was to determine age-specific immunity levels that would ensure elimination of measles when taking into account empirically observed contact patterns.
Methods
We combined estimated immunity levels from serological data in 17 countries with studies of age-specific mixing patterns to derive contact-adjusted immunity levels. We then compared these to case data from the 10 years following the seroprevalence studies to establish a contact-adjusted immunity threshold for elimination. We lastly combined a range of hypothetical immunity profiles with contact data from a wide range of socioeconomic and demographic settings to determine whether they would be sufficient for elimination.
Results
We found that contact-adjusted immunity levels were able to predict whether countries would experience outbreaks in the decade following the serological studies in about 70% of countries. The corresponding threshold level of contact-adjusted immunity was found to be 93%, corresponding to an average basic reproduction number of approximately 14. Testing different scenarios of immunity with this threshold level using contact studies from around the world, we found that 95% immunity would have to be achieved by the age of five and maintained across older age groups to guarantee elimination. This reflects a greater level of immunity required in 5–9-year-olds than established previously.
Conclusions
The immunity levels we found necessary for measles elimination are higher than previous guidance. The importance of achieving high immunity levels in 5–9-year-olds presents both a challenge and an opportunity. While such high levels can be difficult to achieve, school entry provides an opportunity to ensure sufficient vaccination coverage. Combined with observations of contact patterns, further national and sub-national serological studies could serve to highlight key gaps in immunity that need to be filled in order to achieve national and regional measles elimination.
Journal Article
Past as Prologue—Use of Rubella Vaccination Program Lessons to Inform COVID-19 Vaccination
by
Dixon, Meredith G.
,
Reef, Susan E.
,
Zimmerman, Laura A.
in
Babies
,
Clinical and Health Services Delivery and Impact
,
Congenital diseases
2022
The rapid rollout of vaccines against COVID-19 as a key mitigation strategy to end the global pandemic might be informed by lessons learned from rubella vaccine implementation in response to the global rubella epidemic of 1963-1965. That rubella epidemic led to the development of a rubella vaccine that has been introduced in all but 21 countries worldwide and has led to elimination of rubella in 93 countries. Although widespread introduction and use of rubella vaccines was slower than that for COVID-19 vaccines, the process can provide valuable insights for the continued battle against COVID-19. Experiences from the rubella disease control program highlight the critical and evolving elements of a vaccination program, including clearly delineated goals and strategies, regular data-driven revisions to the program based on disease and vaccine safety surveillance, and evaluations to identify the vaccine most capable of achieving disease control targets.
Journal Article
Estimating the burden of rubella virus infection and congenital rubella syndrome through a rubella immunity assessment among pregnant women in the Democratic Republic of the Congo: Potential impact on vaccination policy
2016
Rubella-containing vaccines (RCV) are not yet part of the Democratic Republic of the Congo’s (DRC) vaccination program; however RCV introduction is planned before 2020. Because documentation of DRC’s historical burden of rubella virus infection and congenital rubella syndrome (CRS) has been minimal, estimates of the burden of rubella virus infection and of CRS would help inform the country’s strategy for RCV introduction.
A rubella antibody seroprevalence assessment was conducted using serum collected during 2008–2009 from 1605 pregnant women aged 15–46years attending 7 antenatal care sites in 3 of DRC’s provinces. Estimates of age- and site-specific rubella antibody seroprevalence, population, and fertility rates were used in catalytic models to estimate the incidence of CRS per 100,000 live births and the number of CRS cases born in 2013 in DRC.
Overall 84% (95% CI 82, 86) of the women tested were estimated to be rubella antibody seropositive. The association between age and estimated antibody seroprevalence, adjusting for study site, was not significant (p=0.10). Differences in overall estimated seroprevalence by study site were observed indicating variation by geographical area (p⩽0.03 for all). Estimated seroprevalence was similar for women declaring residence in urban (84%) versus rural (83%) settings (p=0.67). In 2013 for DRC nationally, the estimated incidence of CRS was 69/100,000 live births (95% CI 0, 186), corresponding to 2886 infants (95% CI 342, 6395) born with CRS.
In the 3 provinces, rubella virus transmission is endemic, and most viral exposure and seroconversion occurs before age 15years. However, approximately 10–20% of the women were susceptible to rubella virus infection and thus at risk for having an infant with CRS. This analysis can guide plans for introduction of RCV in DRC. Per World Health Organization recommendations, introduction of RCV should be accompanied by a campaign targeting all children 9months to 14years of age as well as vaccination of women of child bearing age through routine services.
Journal Article
Persistence of Rubella Antibodies after 2 Doses of Measles-Mumps-Rubella Vaccine
by
Reef, Susan E.
,
Sullivan, Bradley J.
,
Forghani, Bagher
in
Adolescent
,
Antibodies
,
Antibodies, Viral - blood
2009
BackgroundSince 1990, most schoolchildren in the United States have received a second dose of measles-mumps-rubella vaccine (MMR2) at kindergarten entry. Elimination of endemic rubella virus circulation in the United States was declared in 2004. The objective of the current study was to evaluate the short- and long-term rubella immunogenicity of MMR2 MethodsAt enrollment in 1994–1995, children (n=307) in a rural Wisconsin health maintenance organization received MMR2 at age 4–6 years. A comparison group of older children (n=306) was vaccinated at age 9–11 years. Serum specimens were collected during a 12-year period. Rubella antibody levels were evaluated by plaque-reduction neutralization (lowest detectable titer, 1:10) ResultsBefore administration of MMR2 in the kindergarten group, 9% of subjects were seronegative, 60% had the lowest detectable titer, and the geometric mean titer (GMT) was 1:13. One month after administration of MMR2, 1% were seronegative, 6% had the lowest detectable titer, and the GMT was 1:42. Four-fold boosts occurred in 62% of subjects, but only 0.3% were immunoglobulin M positive. Twelve years after MMR2 administration, 10% were seronegative, 43% had the lowest detectable titer, and the GMT was 1:17. The middle-school group showed similar patterns ConclusionsRubella antibody response to MMR2 was vigorous, but titers decreased to pre-MMR2 levels after 12 years. Because rubella is a highly epidemic disease, vigilance will be required to assure continued elimination
Journal Article
On the Path to Measles and Rubella Elimination Following Rubella-Containing Vaccine Introduction, 2000–2023, Namibia
by
Reef, Susan E.
,
de Wee, Roselina
,
Shibeshi, Messeret E.
in
Age groups
,
Analysis
,
Combined vaccines
2024
Introduction: The WHO Measles and Rubella Strategic Framework 2021–2030 within the Immunization Agenda 2030 includes both measles and rubella elimination goals and provides guidance to countries for planning and implementing the measles and rubella elimination strategies. Namibia has been implementing measles elimination strategies since 1997. Methods: We reviewed and described the implementation of measles and rubella elimination strategies and the programmatic and epidemiological situation in Namibia during 2000–2023. Namibia introduced a rubella-containing vaccine (RCV) in 2016 as a combined measles–rubella (MR) vaccine using a MR catch-up campaign, targeting a wide age range based on detailed analysis and triangulation of multiple key data sources including MR vaccination coverage, MR case-based surveillance, detailed measles outbreak investigations, and serosurveys. Results: In 2020, estimated MCV1 coverage in Namibia reached 90% and has been sustained at 91% in 2021 and 2022. MCV2 was introduced in 2016, and the estimated MCV2 coverage has steadily increased to 79% in 2022. Following the MCV2 introduction and the implementation of the wide age range MR catch-up campaign in 2016, annual measles and rubella incidence decreased substantially. During 2017–2023, the period following the implementation of the catch-up MR vaccination SIA in 2016, average annual measles incidence per million population in Namibia decreased by 97% from the average during 2010–2016. Similarly, the average annual rubella incidence decreased by 95% from 2010–2016 to 2017–2023. Discussion: Successful implementation of the 2016 wide age range campaign and maintaining high routine immunization coverage likely led to the significant reduction in measles and rubella incidence in Namibia. To sustain the reduction in measles and rubella incidence and attain the elimination targets, Namibia needs to attain and maintain high routine immunization coverage with both doses of the MR vaccine and implement timely and high-quality periodic MR follow-up SIAs. High-quality elimination-standard measles and rubella surveillance will help guide strategies and serve as the basis for the eventual verification of measles and rubella elimination in Namibia according to the WHO-recommended framework.
Journal Article
Progress Toward Rubella and Congenital Rubella Syndrome Control and Elimination — Worldwide, 2012–2020
by
Knapp, Jennifer K.
,
Reef, Susan E.
,
Zimmerman, Laura A.
in
Birth defects
,
Congenital anomalies
,
Congenital defects
2022
Rubella virus is a leading cause of vaccine-preventable birth defects and can cause epidemics. Although rubella virus infection usually produces 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 an infant born with a constellation of birth defects known as congenital rubella syndrome (CRS). A single dose of rubella-containing vaccine (RCV) can provide lifelong protection against rubella (1). The Global Vaccine Action Plan 2011-2020 (GVAP) included a target to achieve elimination of rubella in at least five of the six World Health Organization (WHO) regions* by 2020 (2), and WHO recommends capitalizing on the accelerated measles elimination activities as an opportunity to introduce RCV (1). This report updates a previous report (3) and summarizes global progress toward control and elimination of rubella and CRS from 2012, when accelerated rubella control activities were initiated, through 2020. Among 194 WHO Member States, the number with RCV in their immunization schedules has increased from 132 (68%) in 2012 to 173 (89%) in 2020; 70% of the world's infants were vaccinated against rubella in 2020. Reported rubella cases declined by 48%, from 94,277 in 2012 to 49,136 in 2019, and decreased further to 10,194 in 2020. Rubella elimination has been verified in 93 (48%) of 194 countries including the entire Region of the Americas (AMR). To increase the equity of protection and make further progress to eliminate rubella, it is important that the 21 countries that have not yet done so should introduce RCV. Likewise, countries that have introduced RCV can achieve and maintain rubella elimination with high vaccination coverage and surveillance for rubella and CRS. Four of six WHO regions have established rubella elimination goals; the two WHO regions that have not yet established an elimination goal (the African [AFR] and Eastern Mediterranean [EMR] regions) have expressed a commitment to rubella elimination and should consider establishing a goal.
Journal Article
The path to eradication of rubella
by
Plotkin, Stanley A.
,
Icenogle, Joseph P.
,
Reef, Susan E.
in
Adult
,
Allergy and Immunology
,
Child
2023
Since 1969, rubella and its harmful effect on fetuses infected in utero can be prevented by rubella vaccine, usually given in combination with measles vaccine. The rubella vaccine is highly protective both in children and in adults including women intending to become pregnant. Owing to the use of combined measles and rubella vaccines, congenital rubella infection has been eliminated from the Western Hemisphere and nearly all of Europe. Such combined vaccination is now being applied throughout the world, posing the possibility of eventual rubella eradication. The existence of viruses of animals related to rubella does not appear to be a barrier to eradication of the human virus. However, persistent rubella virus in infants infected in utero and of immunosuppressed patients with granulomas may pose a problem for eradication. Nevertheless, this review posits that eradication of rubella is now feasible if routine vaccination of infants and surveillance for chronic infection are correctly applied.
Journal Article
Progress Toward Rubella and Congenital Rubella Syndrome Control and Elimination — Worldwide, 2000–2018
2019
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.§.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.§.
Journal Article
The Epidemiological Profile of Rubella and Congenital Rubella Syndrome in the United States, 1998–2004: The Evidence for Absence of Endemic Transmission
2006
In 1969, the United States established its national rubella vaccination program. With the success of the program, 32 years later, reports of rubella reached record low numbers. To assess the achievement of elimination of rubella and congenital rubella syndrome (CRS) in the United States, 7 epidemiological criteria were used. Rubella cases reported to the National Notifiable Diseases Surveillance System from 1998 through 2004 and CRS cases reported to the National Congenital Rubella Syndrome Registry from 1998 through 2004 were analyzed. During 1998–2000, the median number of reported rubella cases was 272, whereas, during 2001–2004, the median number reported was 13. The incidence of rubella decreased significantly, from 0.1/100,000 population in 1998 to 0.005/100,000 population in 2004. Since 2001, 5 infants with CRS have been reported—3 were born in 2001, 1 was born in 2003, and 1 was born in 2004. The epidemiological evidence strongly supports the claim that rubella is no longer endemic in the United States. To prevent future rubella outbreaks and CRS cases, current strategies must be maintained.
Journal Article