In Elimination Settings, Measles Antibodies Wane After Vaccination but Not After Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: We conducted a systematic review to assess whether measles humoral immunity wanes in previously infected or vaccinated populations in measles elimination settings. METHODS: After screening 16 822 citations, we identified 9 articles from populations exposed to wild-type measles and 16 articles from vaccinated populations that met our inclusion criteria. RESULTS: Using linear regression, we found that geometric mean titers (GMTs) decreased significantly in individuals who received 2 doses of measles-containing vaccine (MCV) by 121.8 mIU/mL (95% confidence interval [CI], -212.4 to -31.1) per year since vaccination over 1 to 5 years, 53.7 mIU/mL (95% CI, -95.3 to -12.2) 5 to 10 years, 33.2 mIU/mL (95% CI, -62.6 to -3.9), 10 to 15 years, and 24.1 mIU/mL (95% CI, -51.5 to 3.3) 15 to 20 years since vaccination. Decreases in GMT over time were not significant after 1 dose of MCV or after infection. Decreases in the proportion of seropositive individuals over time were not significant after 1 or 2 doses of MCV or after infection. CONCLUSIONS: Measles antibody waning in vaccinated populations should be considered in planning for measles elimination.

The effect of time since measles vaccination and age at first dose on measles vaccine effectiveness - A systematic review.

BACKGROUND: In settings where measles has been eliminated, vaccine-derived immunity may in theory wane more rapidly due to a lack of immune boosting by circulating measles virus. We aimed to assess whether measles vaccine effectiveness (VE) waned over time, and if so, whether differentially in measles-eliminated and measles-endemic settings. METHODS: We performed a systematic literature review of studies that reported VE and time since vaccination with measles-containing vaccine (MCV). We extracted information on case definition (clinical symptoms and/or laboratory diagnosis), method of vaccination status ascertainment (medical record or vaccine registry), as well as any biases which may have arisen from cold chain issues and a lack of an age at first dose of MCV. We then used linear regression to evaluate VE as a function of age at first dose of MCV and time since MCV. RESULTS: After screening 14,782 citations, we identified three full-text articles from measles-eliminated settings and 33 articles from measles-endemic settings. In elimination settings, two-dose VE estimates increased as age at first dose of MCV increased and decreased as time since MCV increased; however, the small number of studies available limited interpretation. In measles-endemic settings, one-dose VE increased by 1.5% (95% CI 0.5, 2.5) for every month increase in age at first dose of MCV. We found no evidence of waning VE in endemic settings. CONCLUSIONS: The paucity of data from measles-eliminated settings indicates that additional studies and approaches (such as studies using proxies including laboratory correlates of protection) are needed to answer the question of whether VE in measles-eliminated settings wanes. Age at first dose of MCV was the most important factor in determining VE. More VE studies need to be conducted in elimination settings, and standards should be developed for information collected and reported in such studies.

The cost saving opportunity of introducing a card review into measles-containing vaccination campaigns.

Measles vaccination is a cost-effective way to prevent infection and reduce mortality and morbidity. However, in countries with fragile routine immunization infrastructure, coverage rates are still low and supplementary immunization campaigns (SIAs) are used to reach previously unvaccinated children. During campaigns, vaccine is generally administered to every child, regardless of their vaccination status and as a result, there is the possibility that a child that is already immune to measles (i.e. who has had 2+ vaccinations) would receive an unnecessary dose, resulting in excess cost. Selective vaccination has been proposed as one solution to this; children who were able to provide documentation of previous vaccination would not be vaccinated repeatedly. While this would result in reduced vaccine and supply cost, it would also require additional staff time and increased social mobilization investment, potentially outweighing the benefits. We utilize Monte Carlo simulation to assess under what conditions a selective vaccination policy would indeed result in net savings. We demonstrate that cost savings are possible in contexts with a high joint probability of an individual child having both 2+ previous measles doses and also an available record. We also find that the magnitude of net cost savings is highly dependent on whether a country is using measles-only or measles-rubella vaccine and on the required skill set of the individual who would review the previous vaccination records.

Combining serological and contact data to derive target immunity levels for achieving and maintaining measles elimination.

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.

Progress Toward Regional Measles Elimination - Worldwide, 2000-2017.

In 2010, the World Health Assembly set three milestones for measles prevention to be achieved by 2015: 1) increase routine coverage with the first dose of measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district; 2) reduce global annual measles incidence to less than five cases per million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (1).* In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan (GVAP),† with the objective of eliminating measles§ in four of the six World Health Organization (WHO) regions by 2015 and in five regions by 2020. Countries in all six WHO regions have adopted goals for measles elimination by 2020. This report describes progress toward global measles control milestones and regional measles elimination goals during 2000-2017 and updates a previous report (2). During 2000-2017, estimated MCV1 coverage increased globally from 72% to 85%; annual reported measles incidence decreased 83%, from 145 to 25 cases per million population; and annual estimated measles deaths decreased 80%, from 545,174 to 109,638. During this period, measles vaccination prevented an estimated 21.1 million deaths. However, measles elimination milestones have not been met, and three regions are experiencing a large measles resurgence. To make further progress, case-based surveillance needs to be strengthened, and coverage with MCV1 and the second dose of measles-containing vaccine (MCV2) needs to increase; in addition, it will be important to maintain political commitment and ensure substantial, sustained investments to achieve global and regional measles elimination goals.

Measles-Rubella Supplementary Immunization Activity Readiness Assessment - India, 2017-2018.

In 2013, during the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR), the 11 SEAR countries* adopted goals to eliminate measles and control rubella and congenital rubella syndrome by 2020† (1). To accelerate progress in India (2,3), a phased§ nationwide supplementary immunization activity (SIA)¶ using measles-rubella vaccine and targeting approximately 410 million children aged 9 months-14 years commenced in 2017 and will be completed by first quarter of 2019. To ensure a high-quality SIA, planning and preparation were monitored using a readiness assessment tool adapted from the WHO global field guide** (4) by the India Ministry of Health and Family Welfare. This report describes the results and experience gained from conducting SIA readiness assessments in 24 districts of three Indian states (Andhra Pradesh, Kerala, and Telangana) during the second phase of the SIA. In each selected area, assessments were conducted 4-6 weeks and 1-2 weeks before the scheduled SIA. At the first assessment, none of the states and districts were on track with preparations for the SIA. However, at the second assessment, two (67%) states and 21 (88%) districts were on track. The SIA readiness assessment identified several preparedness gaps; early assessment results were immediately communicated to authorities and led to necessary corrective actions to ensure high-quality SIA implementation.

Progress Toward Rubella and Congenital Rubella Syndrome Control - South-East Asia Region, 2000-2016.

In 2013, the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR)* adopted the goal of elimination of measles and control† of rubella and congenital rubella syndrome (CRS) by 2020 (1). Rubella is the leading vaccine-preventable cause of birth defects. Although rubella typically causes a mild fever and rash in children and adults, rubella virus infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, or a constellation of congenital malformations known as CRS, commonly including visual, auditory, and/or cardiac defects, and developmental delay (2). Rubella and CRS control capitalizes on the momentum created by pursuing measles elimination because the efforts are programmatically linked. Rubella-containing vaccine (RCV) is administered as a combined measles and rubella vaccine, and rubella cases are detected through case-based surveillance for measles or fever and rash illness (3). This report summarizes progress toward rubella and CRS control in SEAR during 2000-2016. Estimated coverage with a first RCV dose (RCV1) increased from 3% of the birth cohort in 2000 to 15% in 2016 because of RCV introduction in six countries. RCV1 coverage is expected to increase rapidly with the phased introduction of RCV in India and Indonesia beginning in 2017; these countries are home to 83% of the SEAR birth cohort. During 2000-2016, approximately 83 million persons were vaccinated through 13 supplemental immunization activities (SIAs) conducted in eight countries. During 2010-2016, reported rubella incidence decreased by 37%, from 8.6 to 5.4 cases per 1 million population, and four countries (Bangladesh, Maldives, Sri Lanka, and Thailand) reported a decrease in incidence of ≥95% since 2010. To achieve rubella and CRS control in SEAR, sustained investment to increase routine RCV coverage, periodic high-quality SIAs to close immunity gaps, and strengthened rubella and CRS surveillance are needed.

Progress Toward Measles Elimination - Western Pacific Region, 2013-2017.

In 2005, the Regional Committee for the World Health Organization (WHO) Western Pacific Region (WPR)* established a goal for measles elimination† by 2012 (1). To achieve this goal, the 37 WPR countries and areas implemented the recommended strategies in the WPR Plan of Action for Measles Elimination (2) and the Field Guidelines for Measles Elimination (3). The strategies include 1) achieving and maintaining ≥95% coverage with 2 doses of measles-containing vaccine (MCV) through routine immunization services and supplementary immunization activities (SIAs), when required; 2) conducting high-quality case-based measles surveillance, including timely and accurate testing of specimens to confirm or discard suspected cases and detect measles virus for genotyping and molecular analysis; and 3) establishing and maintaining measles outbreak preparedness to ensure rapid response and appropriate case management. This report updates the previous report (4) and describes progress toward measles elimination in WPR during 2013-2017. During 2013-2016, estimated regional coverage with the first MCV dose (MCV1) decreased from 97% to 96%, and coverage with the routine second MCV dose (MCV2) increased from 91% to 93%. Eighteen (50%) countries achieved ≥95% MCV1 coverage in 2016. Seven (39%) of 18 nationwide SIAs during 2013-2017 reported achieving ≥95% administrative coverage. After a record low of 5.9 cases per million population in 2012, measles incidence increased during 2013-2016 to a high of 68.9 in 2014, because of outbreaks in the Philippines and Vietnam, as well as increased incidence in China, and then declined to 5.2 in 2017. To achieve measles elimination in WPR, additional measures are needed to strengthen immunization programs to achieve high population immunity, maintain high-quality surveillance for rapid case detection and confirmation, and ensure outbreak preparedness and prompt response to contain outbreaks.

Progress in Rubella and Congenital Rubella Syndrome Control and Elimination - Worldwide, 2000-2016.

Although rubella virus infection usually causes a mild fever and rash illness in children and adults, infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, stillbirth, or infants with a constellation of congenital malformations known as congenital rubella syndrome (CRS) (1). Rubella is a leading vaccine-preventable cause of birth defects. Preventing these adverse pregnancy outcomes is the focus of rubella vaccination programs. In 2011, the World Health Organization (WHO) updated guidance on the preferred strategy for introduction of rubella-containing vaccine (RCV) into national immunization schedules and recommended an initial vaccination campaign, usually targeting children aged 9 months-14 years (1). The Global Vaccine Action Plan 2011-2020 (GVAP), endorsed by the World Health Assembly in 2012, includes goals to eliminate rubella in at least five of the six WHO regions by 2020 (2). This report updates a previous report (3) and summarizes global progress toward rubella and CRS control and elimination from 2000 to 2016. As of December 2016, 152 (78%) of 194 countries had introduced RCV into the national immunization schedule, representing an increase of 53 countries since 2000, including 20 countries that introduced RCV after 2012.

Progress Toward Regional Measles Elimination - Worldwide, 2000-2016.

The fourth United Nations Millennium Development Goal, adopted in 2000, set a target to reduce child mortality by two thirds by 2015. One indicator of progress toward this target was measles vaccination coverage (1). In 2010, the World Health Assembly (WHA) set three milestones for measles control by 2015: 1) increase routine coverage with the first dose of a measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district; 2) reduce global annual measles incidence to <5 cases per million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (2).* In 2012, WHA endorsed the Global Vaccine Action Plan,† with the objective of eliminating measles in four World Health Organization (WHO) regions by 2015 and in five regions by 2020. Countries in all six WHO regions have adopted goals for measles elimination by or before 2020. Measles elimination is defined as the absence of endemic measles virus transmission in a region or other defined geographic area for ≥12 months, in the presence of a high quality surveillance system that meets targets of key performance indicators. This report updates a previous report (3) and describes progress toward global measles control milestones and regional measles elimination goals during 2000-2016. During this period, annual reported measles incidence decreased 87%, from 145 to 19 cases per million persons, and annual estimated measles deaths decreased 84%, from 550,100 to 89,780; measles vaccination prevented an estimated 20.4 million deaths. However, the 2015 milestones have not yet been met; only one WHO region has been verified as having eliminated measles. Improved implementation of elimination strategies by countries and their partners is needed, with focus on increasing vaccination coverage through substantial and sustained additional investments in health systems, strengthening surveillance systems, using surveillance data to drive programmatic actions, securing political commitment, and raising the visibility of measles elimination goals.

Progress Toward Measles Elimination - Bangladesh, 2000-2016.

In 2013, at the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR), a regional goal was established to eliminate measles and control rubella and congenital rubella syndrome* by 2020 (1). WHO-recommended measles elimination strategies in SEAR countries include 1) achieving and maintaining ≥95% coverage with 2 doses of measles-containing vaccine (MCV) in every district, delivered through the routine immunization program or through supplementary immunization activities (SIAs)†; 2) developing and sustaining a sensitive and timely measles case-based surveillance system that meets targets for recommended performance indicators; and 3) developing and maintaining an accredited measles laboratory network (2). In 2014, Bangladesh, one of 11 countries in SEAR, adopted a national goal for measles elimination by 2018 (2,3). This report describes progress and challenges toward measles elimination in Bangladesh during 2000-2016. Estimated coverage with the first MCV dose (MCV1) increased from 74% in 2000 to 94% in 2016. The second MCV dose (MCV2) was introduced in 2012, and MCV2 coverage increased from 35% in 2013 to 93% in 2016. During 2000-2016, approximately 108.9 million children received MCV during three nationwide SIAs conducted in phases. During 2000-2016, reported confirmed measles incidence decreased 82%, from 34.2 to 6.1 per million population. However, in 2016, 56% of districts did not meet the surveillance performance target of ≥2 discarded nonmeasles, nonrubella cases§ per 100,000 population. Additional measures that include increasing MCV1 and MCV2 coverage to ≥95% in all districts with additional strategies for hard-to-reach populations, increasing sensitivity of measles case-based surveillance, and ensuring timely transport of specimens to the national laboratory will help achieve measles elimination.

Progress Toward Measles Elimination - African Region, 2013-2016.

In 2011, the 46 World Health Organization (WHO) African Region (AFR) member states established a goal of measles elimination* by 2020, by achieving 1) ≥95% coverage of their target populations with the first dose of measles-containing vaccine (MCV1) at national and district levels; 2) ≥95% coverage with measles-containing vaccine (MCV) per district during supplemental immunization activities (SIAs); and 3) confirmed measles incidence of <1 case per 1 million population in all countries (1). Two key surveillance performance indicator targets include 1) investigating ≥2 cases of nonmeasles febrile rash illness per 100,000 population annually, and 2) obtaining a blood specimen from ≥1 suspected measles case in ≥80% of districts annually (2). This report updates the previous report (3) and describes progress toward measles elimination in AFR during 2013-2016. Estimated regional MCV1 coverage† increased from 71% in 2013 to 74% in 2015.§ Seven (15%) countries achieved ≥95% MCV1 coverage in 2015.¶ The number of countries providing a routine second MCV dose (MCV2) increased from 11 (24%) in 2013 to 23 (49%) in 2015. Forty-one (79%) of 52 SIAs** during 2013-2016 reported ≥95% coverage. Both surveillance targets were met in 19 (40%) countries in 2016. Confirmed measles incidence in AFR decreased from 76.3 per 1 million population to 27.9 during 2013-2016. To eliminate measles by 2020, AFR countries and partners need to 1) achieve ≥95% 2-dose MCV coverage through improved immunization services, including second dose (MCV2) introduction; 2) improve SIA quality by preparing 12-15 months in advance, and using readiness, intra-SIA, and post-SIA assessment tools; 3) fully implement elimination-standard surveillance††; 4) conduct annual district-level risk assessments; and 5) establish national committees and a regional commission for the verification of measles elimination.

Development of a District-Level Programmatic Assessment Tool for Risk of Measles Virus Transmission.

All six World Health Organization (WHO) regions have now set goals for measles elimination by or before 2020. To prioritize measles elimination efforts and use available resources efficiently, there is a need to identify at-risk areas that are offtrack from meeting performance targets and require strengthening of programmatic efforts. This article describes the development of a WHO measles programmatic risk assessment tool to be used for monitoring, guiding, and sustaining measles elimination efforts at the subnational level. We outline the tool development process; the tool specifications and requirements for data inputs; the framework of risk categories, indicators, and scoring; and the risk category assignment. Overall risk was assessed as a function of indicator scores that fall into four main categories: population immunity, surveillance quality, program performance, and threat assessment. On the basis of the overall score, the tool assigns each district a risk of either low, medium, high, or very high. The cut-off criteria for the risk assignment categories were based on the distribution of scores from all possible combinations of individual indicator cutoffs. The results may be used for advocacy to communicate risk to policymakers, mobilize resources for corrective actions, manage population immunity, and prioritize programmatic activities. Ongoing evaluation of indicators will be needed to evaluate programmatic performance and plan risk mitigation activities effectively. The availability of a comprehensive tool that can identify at-risk districts will enhance efforts to prioritize resources and implement strategies for achieving the Global Vaccine Action Plan goals for measles elimination.

Progress Toward Regional Measles Elimination - Worldwide, 2000-2015.

Adopted in 2000, United Nations Millennium Development Goal 4 set a target to reduce child mortality by two thirds by 2015, with measles vaccination coverage as one of the progress indicators. In 2010, the World Health Assembly (WHA) set three milestones for measles control by 2015: 1) increase routine coverage with the first dose of measles-containing vaccine (MCV1) for children aged 1 year to ≥90% nationally and ≥80% in every district; 2) reduce global annual measles incidence to <5 cases per 1 million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (1,2).* In 2012, WHA endorsed the Global Vaccine Action Plan† with the objective to eliminate measles in four World Health Organization (WHO) regions by 2015. Countries in all six WHO regions have adopted measles elimination goals. Measles elimination is the absence of endemic measles transmission in a region or other defined geographical area for ≥12 months in the presence of a well performing surveillance system. This report updates a previous report (3) and describes progress toward global measles control milestones and regional measles elimination goals during 2000-2015. During this period, annual reported measles incidence decreased 75%, from 146 to 36 cases per 1 million persons, and annual estimated measles deaths decreased 79%, from 651,600 to 134,200. However, none of the 2015 milestones or elimination goals were met. Countries and their partners need to act urgently to secure political commitment, raise the visibility of measles, increase vaccination coverage, strengthen surveillance, and mitigate the threat of decreasing resources for immunization once polio eradication is achieved.

Real-Time Monitoring of Vaccination Campaign Performance Using Mobile Phones - Nepal, 2016.

In 2012, the Global Vaccine Action Plan* established a goal to achieve measles and rubella elimination in five of the six World Health Organization (WHO) regions (194 countries) by 2020 (1). Measles elimination strategies aim to achieve ≥95% coverage with 2 routine doses of measles-containing vaccine (2), and implement supplementary immunization activities (SIAs)† in settings where routine coverage is low or where there are subpopulations at high risk. To ensure SIA quality and to achieve ≥95% SIA coverage nationally, rapid convenience monitoring (RCM) is used during or immediately after SIAs (3,4). The objective of RCM is to find unvaccinated children and to identify reasons for nonvaccination in areas with persons at high risk, to enable immediate implementation of corrective actions (e.g., reassigning teams to poorly vaccinated areas, modifying the timing of vaccination, or conducting mop-up vaccination activities). This report describes pilot testing of RCM using mobile phones (RCM-MP) during the second phase of an SIA in Nepal in 2016. Use of RCM-MP resulted in 87% timeliness and 94% completeness of data reporting and found that, although 95% of children were vaccinated, 42% of areas required corrective vaccination activities. RCM-MP challenges included connecting to mobile networks, small phone screen size, and capturing Global Positioning System (GPS) coordinates. Nonetheless, use of RCM-MP led to faster data transmission, analysis, and decision-making and to increased accountability among levels of the health system.

Progress Toward Measles Elimination - Nepal, 2007-2014.

In 2013, the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region (SEAR) established a goal to eliminate measles and to control rubella and congenital rubella syndrome (CRS) in SEAR by 2020. Current recommended measles elimination strategies in the region include 1) achieving and maintaining ≥95% coverage with 2 doses of measles-containing vaccine (MCV) in every district, delivered through the routine immunization program or through supplementary immunization activities (SIAs); 2) developing and sustaining a sensitive and timely measles case-based surveillance system that meets minimum recommended performance indicators; 3) developing and maintaining an accredited measles laboratory network; and 4) achieving timely identification, investigation, and response to measles outbreaks. In 2013, Nepal, one of the 11 SEAR member states, adopted a goal for national measles elimination by 2019. This report updates a previous report and summarizes progress toward measles elimination in Nepal during 2007-2014. During 2007-2014, estimated coverage with the first MCV dose (MCV1) increased from 81% to 88%. Approximately 3.9 and 9.7 million children were vaccinated in SIAs conducted in 2008 and 2014, respectively. Reported suspected measles incidence declined by 13% during 2007-2014, from 54 to 47 cases per 1 million population. However, in 2014, 81% of districts did not meet the measles case-based surveillance performance indicator target of ≥2 discarded non-measles cases per 100,000 population per year. To achieve and maintain measles elimination, additional measures are needed to strengthen routine immunization services to increase coverage with MCV1 and a recently introduced second dose of MCV (MCV2) to ≥95% in all districts, and to enhance sensitivity of measles case-based surveillance by adopting a more sensitive case definition, expanding case-based surveillance sites nationwide, and ensuring timely transport of specimens to the accredited national laboratory.

Using Seroprevalence and Immunisation Coverage Data to Estimate the Global Burden of Congenital Rubella Syndrome, 1996-2010: A Systematic Review.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Progress toward regional measles elimination - worldwide, 2000-2014.

In 2000, the United Nations General Assembly adopted the Millennium Development Goals (MDG), with MDG4 being a two-thirds reduction in child mortality by 2015, and with measles vaccination coverage being one of the three indicators of progress toward this goal.* In 2010, the World Health Assembly established three milestones for measles control by 2015: 1) increase routine coverage with the first dose of measles-containing vaccine (MCV1) for children aged 1 year to ≥90% nationally and ≥80% in every district; 2) reduce global annual measles incidence to fewer than five cases per million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (1).† In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan§ with the objective to eliminate measles in four World Health Organization (WHO) regions by 2015. WHO member states in all six WHO regions have adopted measles elimination goals. This report updates the 2000­2013 report (2) and describes progress toward global control and regional measles elimination during 2000­2014. During this period, annual reported measles incidence declined 73% worldwide, from 146 to 40 cases per million population, and annual estimated measles deaths declined 79%, from 546,800 to 114,900. However, progress toward the 2015 milestones and elimination goals has slowed markedly since 2010. To resume progress toward milestones and goals for measles elimination, a review of current strategies and challenges to improving program performance is needed, and countries and their partners need to raise the visibility of measles elimination, address barriers to measles vaccination, and make substantial and sustained additional investments in strengthening health systems.

Global Progress Toward Rubella and Congenital Rubella Syndrome Control and Elimination - 2000-2014.

Rubella virus usually causes a mild fever and rash in children and adults. However, infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, stillbirth, or a constellation of congenital malformations known as congenital rubella syndrome (CRS). In 2011, the World Health Organization (WHO) updated guidance on the preferred strategy for introduction of rubella-containing vaccine (RCV) into national routine immunization schedules, including an initial vaccination campaign usually targeting children aged 9 months-15 years . The Global Vaccine Action Plan endorsed by the World Health Assembly in 2012 and the Global Measles and Rubella Strategic Plan (2012-2020) published by Measles and Rubella Initiative partners in 2012 both include goals to eliminate rubella and CRS in at least two WHO regions by 2015, and at least five WHO regions by 2020 (2,3). This report updates a previous report and summarizes global progress toward rubella and CRS control and elimination during 2000-2014. As of December 2014, RCV had been introduced in 140 (72%) countries, an increase from 99 (51%) countries in 2000 (for this report, WHO member states are referred to as countries). Reported rubella cases declined 95%, from 670,894 cases in 102 countries in 2000 to 33,068 cases in 162 countries in 2014, although reporting is inconsistent. To achieve the 2020 Global Vaccine Action Plan rubella and CRS elimination goals, RCV introduction needs to continue as country criteria indicating readiness are met, and rubella and CRS surveillance need to be strengthened to ensure that progress toward elimination can be measured.

Progress Toward Measles Elimination - South-East Asia Region, 2003-2013.

In 2013, the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region adopted the goal of measles elimination and rubella and congenital rubella syndrome control by 2020 after rigorous prior consultations. The recommended strategies include 1) achieving and maintaining ≥95% coverage with 2 doses of measles- and rubella-containing vaccine in every district through routine or supplementary immunization activities (SIAs); 2) developing and sustaining a sensitive and timely case-based measles surveillance system that meets recommended performance indicators; 3) developing and maintaining an accredited measles laboratory network; and 4) achieving timely identification, investigation, and response to measles outbreaks. This report updates previous reports and summarizes progress toward measles elimination in the South-East Asia Region during 2003-2013. Within the region, coverage with the first dose of a measles-containing vaccine (MCV1) increased from 67% to 78%; an estimated 286 million children (95% of the target population) were vaccinated in SIAs; measles incidence decreased 73%, from 59 to 16 cases per million population; and estimated measles deaths decreased 63%. To achieve measles elimination in the region, additional efforts are needed in countries with <95% 2-dose routine MCV coverage, particularly in India and Indonesia, to strengthen routine immunization services, conduct periodic high-quality SIAs, and strengthen measles case-based surveillance and laboratory diagnosis of measles.