Feasibility assessment of measles and rubella eradication

This report addresses the epidemiological aspects and feasibility of measles and rubella eradication and the potential resource requirements in response to the request of the Director-General at the Seventieth World Health Assembly held on May 31, 2017. A guiding principle is that the path toward measles and rubella eradication should serve to strengthen primary health care, promote universal health coverage, and be a pathfinder for new vision and strategy for immunization over the next decade as laid out in the Immunization Agenda 2030. Specifically, this report: 1) highlights the importance of measles and rubella as global health priorities; 2) reviews the current global measles and rubella situation; 3) summarizes prior assessments of the feasibility of measles and rubella eradication; 4) assesses the progress and challenges in achieving regional measles and rubella elimination; 5) assesses additional considerations for measles and rubella eradication, including the results of modelling and economic analyses; 6) assesses the implications of establishing a measles and rubella eradication goal and the process for setting an eradication target date; 7) proposes a framework for determining preconditions for setting a target date for measles and rubella eradication and how these preconditions should be understood and used; and 8) concludes with recommendations endorsed by SAGE.     

Measles and rubella eradication

This article discusses concepts of eradication, some issues relating to vertical and horizontal public health programs, some current issues relating to measles and rubella, and what we need to do about them. It concludes that measles and rubella/CRS can and should be eradicated. A target date should be established in 2020 (or before). Eradication can only be accomplished in the context of strengthening ongoing immunization services and strengthening surveillance so it can guide activities. Additional resources will be required to achieve the goal.     

Research priorities for accelerating progress toward measles and rubella elimination identified by a cross-sectional web-based survey

BackgroundIn 2012, the World Health Assembly endorsed the Global Vaccine Action Plan (GVAP) that set a target to eliminate measles and rubella in five of the six World Health Organization (WHO) regions by 2020. Significant progress has been made toward achieving this goal through intensive efforts by countries and Measles & Rubella Initiative (M&RI) partners. Accelerating progress will require evidence-based approaches to improve implementation of the core strategies in the Global Measles and Rubella Strategic Plan. The M&RI Research and Innovation Working Group (R&IWG) conducted a web-based survey as part of a process to identify measles and rubella research priorities. Survey findings were used to inform discussions during a meeting of experts convened by the M&RI at the Pan American Health Organization in November 2016.MethodsThe cross-sectional web-based survey of scientific and programmatic experts included questions in four main topic areas: (1) epidemiology and economics (epidemiology); (2) new tools for surveillance, vaccine delivery, and laboratory testing (new tools); (3) immunization strategies and outbreak response (strategies); and (4) vaccine demand and communications (demand). Analyses were stratified by the six WHO regions and by global, regional, or national/sub-national level of respondents.ResultsThe six highest priority research questions selected by survey respondents from the four topic areas were the following: (1) What are the causes of outbreaks in settings with high reported vaccination coverage? (epidemiology); (2) Can affordable diagnostic tests be developed to confirm measles and rubella cases rapidly and accurately at the point of care? (new tools); (3) What are effective strategies for increasing coverage of the routine first dose of measles vaccine administered at 9 or 12 months? (strategies); (4) What are effective strategies for increasing coverage of the second dose given after the first year of life? (strategies); (5) How can communities best be engaged in planning, implementing and monitoring health services including vaccinations? (demand); (6) What capacity building is needed for health workers to be able to identify and work more effectively with community leaders? (demand). Research priorities varied by region and by global/regional/national levels for all topic areas.ConclusionsResearch and innovation will be critical to make further progress toward achieving the GVAP measles and rubella elimination goals. The results of this survey can be used to inform decision-making for investments in research activities at the global, regional, and national levels.     

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.     

Global landscape of measles and rubella surveillance

BackgroundAll six World Health Organization (WHO) regions have committed to eliminate measles, and three WHO regions have committed to eliminate rubella. One of the key tenets of measles and rubella elimination is to have a strong surveillance system in place. The presence of a case-based measles and rubella surveillance system that is national, population-based, provides laboratory confirmation, and directs action, is one of the requirements for elimination-standard surveillance.MethodsIn order to understand the global landscape for measles and rubella surveillance, a questionnaire was sent to all 194 WHO member states (herein referred to as countries) requesting information on how surveillance was conducted for measles, rubella, and congenital rubella syndrome. Data were supplemented with information provided to WHO through other reporting mechanisms and by national policy documents available to the public. Frequencies and percentages were calculated.ResultsData were available to review from 164 (85%) countries, although not every country responded to every question. Case-based, population-based, national surveillance with laboratory confirmation was reported to be conducted in 136 (86%) of 158 countries for measles and 122 (77%) of 158 countries for rubella. Congenital rubella syndrome surveillance was reported to be conducted by 126 (77%) of 163 countries. Gaps were noted in the quality of measles-rubella surveillance conducted, and 26 (16%) of 158 countries reported not including all healthcare providers as mandatory reporters.ConclusionsMany countries reported having some of the essential components in place to conduct elimination-standard surveillance for measles and rubella; however, in order to achieve elimination, the quality of surveillance needs to improve to detect all cases. In those countries without these essential components of elimination-standard surveillance, the first step is to implement these components.     

Progress and challenges in measles and rubella elimination in the WHO European Region

IntroductionDespite availability of safe and cost-effective vaccines to prevent it, measles remains one of the significant causes of death among children under five years of age globally. The World Health Organization (WHO) European Region has seen a drastic decline in measles and rubella cases in recent years, and a few of the once common measles genotypes are no longer detected. Buoyed by this success, all Member States of the Region reconfirmed their commitment in 2010 to eliminating measles and rubella, and made this a central objective of the European Vaccine Action Plan 2015–2020 (EVAP). Nevertheless, sporadic outbreaks continue, recently affecting primarily adolescents and young adults with no vaccination or an incomplete vaccination history. The European Regional Verification Commission for Measles and Rubella Elimination was established in 2011 to evaluate the status of measles and rubella elimination based on documentation submitted annually by each country’s national verification committee.DiscussionEach country’s commitment to eliminate measles and rubella is influenced by competing health priorities, and in some cases lack of capacity and resources. All countries need to improve case-base surveillance for both measles and rubella, ensure documentation of each outbreak and strengthen the link between epidemiology and laboratory data. Achieving high coverage with measles- and rubella-containing vaccines will require a multisectoral approach to address the root causes of lower uptake in identified communities including service delivery challenges or vaccine safety concerns caused by circulating myths about vaccination.ConclusionsThe WHO European Region has made steady progress towards eliminating measles and rubella and over half of the countries interrupted endemic transmission of both diseases by 2015. The programmatic challenges in disease surveillance, vaccination service delivery and communication in the remaining endemic countries should be addressed through periodic evaluation of the strategies by all stakeholders and exploring additional opportunities to accelerate the ongoing elimination activities.     

A review of testing used in seroprevalence studies on measles and rubella

Seroprevalence studies are an essential tool to monitor the efficacy of vaccination programmes, to understand population immunity and to identify populations at higher risk of infection. An overarching review of all aspects of seroprevalence studies for measles and rubella published between 1998 and June 2014 was undertaken and the findings reported elsewhere. This paper details the considerable variation in the testing formats identified in the review. Apart from serum/plasma samples, testing of oral fluid, breast milk, dry blood spots and capillary whole blood were reported. Numerous different commercial assays were employed, including microtitre plate assays, automated immunoassays and classical haemagglutination inhibition and neutralisation assays. A total of 29 of the 68 (43%) measles and 14 of the 58 (24%) rubella studies reported qualitative test results. Very little information on the testing environment, including quality assurance mechanisms used, was provided. Due to the large numbers of testing systems, the diversity of sample types used and the difficulties in accurate quantification of antibody levels, the results reported in individual studies were not necessarily comparable. Further efforts to standardise seroprevalence studies may overcome this deficiency.     

The strategy for prevention of measles and rubella prevalence with measles–rubella (MR) vaccine in Japan

To eliminate the indigenous measles and rubella virus by 2012 in Japan, the strategy for prevention of measles and rubella prevalence with measles-rubella (MR) vaccine was proposed. Since the vast majority of 1-year old infants are susceptible to measles and rubella, the first MR vaccine should be administered at 1-year old to sustain the herd immunity. Since significant elevation of measles and rubella antibody titers was estimated in a half of children after the second dose, the second dose of MR vaccine within 1 year before elementary school entry is the effective maneuver. Moreover, supplement MR vaccination to the teenage group and 20–29 years’ group might be necessary, because the mean measles antibody titers in this group were significantly lower compared with those in the older individuals’ groups.     

A 16-year review of seroprevalence studies on measles and rubella

The determination of the seroprevalence of vaccine-preventable diseases is critical in monitoring the efficacy of vaccination programmes and to assess the gaps in population immunity but requires extensive organisation and is time and resource intensive. The results of the studies are frequently reported in peer-reviewed scientific, government and non-government publications. A review of scientific literature was undertaken to advise the development of WHO guidelines for the assessment of measles and rubella seroprevalence. A search of the National Library of Medicine’s PubMed online publications using key words of ‘measles’, ‘rubella’, combined with ‘serosurvey’, ‘seroprevalence’, ‘immunity’ and ‘population immunity’ was conducted. A total of 97 articles published between January 1998 and June 2014 were retrieved, 68 describing serosurveys for measles and 58 serosurveys for rubella, conducted in 37 and 36 different countries respectively. Only 13 (19%) and 8 (14%) respectively were UN classified “least developed countries”. The study sample varied markedly and included combinations of male and female infants, children, adolescents and adults. The study sizes also varied with 28% and 33% of measles and rubella studies respectively, having greater than 2000 participants. Microtitre plate enzyme immunoassays were used in 52 (76%) measles studies and 40 (69%) rubella studies. A total of 39 (57%) measles and 44 (76%) rubella studies reported quantitative test results. Seroprevalence ranged from 60.8% to 95.9% for measles and 53.0% to 99.3% for rubella studies. The review highlighted that infants lost maternally-acquired immunity within 9 months of birth and were unprotected until vaccination. Two groups at higher risk of infection were identified: young adults between the ages of 15 and 30 years and immigrants.     

2014年新疆克拉玛依市健康人群麻疹、风疹抗体水平监测分析

目的 了解克拉玛依市人群麻疹、风疹抗体水平,有针对性地开展麻疹、风疹免疫预防工作,有效控制麻疹、风疹的发生和流行,实现消除麻疹的目标。方法 按照分层随机抽样方法,采集0～60岁健康人群1 056人份血样,采用ELISA方法,定量检测麻疹抗体、风疹抗体。结果 人群麻疹抗体阳性率97.54%、风疹抗体阳性率87.22%,抗体几何平均浓度(Geometric Mean Concentration,GMC) 麻疹、风疹分别为:1 220.10 mIU/ml、68.23 IU/ml,不同人群麻疹、风疹抗体阳性率差异均有统计学意义（麻疹χ2＝20.170,风疹χ2＝17.090,P均＜0.05）;不同地区麻疹抗体阳性率在95%以上、保护率在65%～75%之间,风疹抗体阳性率在75%～94%之间,不同地区风疹抗体阳性率差异有统计学意义（χ2 = 31.106;P＜0.001）;不同免疫史风疹抗体阳性水平差异有统计学意义（χ2＝30.254,P＜0.001）。结论 克拉玛依市麻疹人群抗体阳性率总体保持在较高水平,风疹抗体阳性率水平略低,乌尔禾区和部分年龄组风疹阳性率较低。应重点加强地区及重点人群疫苗预防接种管理,必要时开展人群查漏补种免疫。     

昌平区2006年麻疹和风疹疑似病例血清学检测结果分析

目的:了解昌平区麻疹、风疹疑似病例的血清学实验室诊断符合率和血清流行病学特征,为进一步提高麻疹、风疹的病例诊断提供依据。方法:应用酶联免疫吸附试验检测血清标本中麻疹或风疹IgM抗体。结果:2006年共检测麻疹疑似病例血清175例,检出麻疹IgM抗体阳性55例,实验室诊断符合率为31.4%,在其余麻疹IgM抗体阴性的120例病例中检出风疹IgM抗体阳性34例,检出率为28.3%。检测风疹疑似病例血清172例,检出风疹IgM抗体阳性75例,实验室诊断符合率为43.6%,在其余风疹IgM抗体阴性的97例病例中检出麻疹IgM抗体阳性3例,检出率为3.1%。麻疹、风疹疑似病例与实验室诊断病例的发病时间均集中在3~6月份;年龄均以20~24岁组最多;外地户籍和无疫苗接种史或接种史不详的麻疹和风疹病例占80%以上。结论:我区麻疹疑似病例实验室诊断阳性符合率为31.4%,低于国内相关报道[1]。风疹实验室诊断阳性符合率为43.6%,与国内相关报道相同[2],存在误诊漏诊现象;外地户籍和无疫苗接种史或接种史不详的麻疹和风疹病例占80%以上。     

Successful seroresponses to measles and rubella following aerosolized Triviraten vaccine,but poor response to aerosolized mumps (Rubini) component: Comparisons with injected MMR

Seroresponses to measles, rubella and mumps were evaluated following the injection of MMR II and injection or aerosol administration of Triviraten in young adults. Response to aerosolized Rubini mumps strain was a focus of interest, given robust responses to aerosolized mumps vaccine (Leningrad-Zagreb strain) in a prior study using aerosolized MMR vaccine. The aerosolized Edmonston-Zagreb (EZ) measles vaccine was significantly more immunogenic than injected EZ vaccine, and comparable to results following injected Moraten measles vaccine having twice the dosage. Responses to rubella were comparable in the three MMR study groups. Aerosolized Rubini vaccine was very highly and unexpectedly less immunogenic than either injected Rubini or Jeryl-Lyn strains. The high attenuation of Rubini vaccine appears to have limited its affinity for respiratory tract receptors, which may underlie its lack of clinical effectiveness.     

Humoral immunogenicity to measles,rubella, and varicella-zoster vaccines in biliary atresia children

To investigate the humoral immune response to measles, rubella, and varicella-zoster virus (VZV) vaccines in biliary atresia (BA) children before liver transplantation, we conducted the cross-sectional designed study. Fifty BA children (age, 3.6 ± 0.2 years; 24 girls) who had not yet received liver transplantation, and another 150 healthy controls (age, 4.0 ± 0.1 years; 78 girls) were recruited into this study to evaluate their primary humoral immune response to measles, rubella, and VZV vaccines. All of these BA children (n = 50) and controls (n = 150) received one dose of measles, one dose of measles–mumps–rubella (MMR), and one dose of VZV vaccine before our assessment. Serum samples were collected at least 1 month after the vaccination and serum immunoglobulin G (IgG) antibody to measles, rubella, and VZV were then determined by qualitative enzyme-linked immune-sorbent assay. The prevalence of seropositive rate of measles IgG antibody (84% vs. 96.7%; P = 0.002), rubella (82.0% vs. 98.7%; P < 0.001), and VZV (74% vs. 95.3%; P < 0.001) were significantly different between BA children and the controls after regular measles, MMR, and VZV vaccination before 2 years of age. In those BA children with seronegative VZV antibody after vaccination, two had VZV infection after the liver transplantation. This study indicated that humoral immunity to rubella, measles and VZV vaccines are significantly lower in BA children than the normal population by standard vaccine schedule.     

Seroprevalence of measles and rubella antibodies in pregnant women Haiti, 2012

Background

Haiti had set a national goal to eliminate measles and rubella, as well as congenital rubella syndrome (CRS) by 2010. A 2007–2008 nationwide measles and rubella vaccination campaign targeting 1–19 years, however, reached only 79% of the target population. To assess whether population immunity was adequate to support elimination, we conducted a national serosurvey.

Methods

We systematically selected 740 serum specimens collected from pregnant women in a 2012 national antenatal HIV sentinel serosurvey across four age strata: 15–19, 20–24, 25–29 and 30–39 years. Sera were tested for measles and rubella specific immunoglobulin G antibodies (IgG) using commercial immunoassays. We classified sera as seropositive, seronegative or indeterminate per manufacturer's instructions, and analyzed seroprevalence according to age strata, and rural or urban residence. We assessed immunity by estimating antibody concentrations in international units per milliliter (IU/mL) for seropositive and indeterminate sera. Measles IgG concentrations >0.12 IU/mL and rubella IgG concentrations >10 IU/mL were considered clinically protective.

Results

Of 740 sera, 696 (94.1%) were seropositive and 20 (2.7%) were indeterminate for measles IgG; overall 716 (96.8%) sera had IgG concentrations >0.12 IU/mL. For rubella IgG, 691 (93.4%) sera were seropositive and 1 (0.1%) was indeterminate; a total of 687 (92.8%) had IgG concentrations >10 IU/mL. Measles seropositivity varied across age strata (p = 0.003); seropositivity increased from 88.6% among 15–19 year olds to 98.4% among 30–39 year olds (Cochran–Armitage trend test ≤ 0.0001). Rubella seropositivity did not differ across age strata. There were no statistically significant differences in measles or rubella seropositivity by urban versus rural residence.

Conclusion

Despite previous low vaccination coverage for measles, results from this serosurvey indicate high levels of measles and rubella seropositivity in pregnant women, and contribute to the evidence for measles, rubella and CRS elimination from Haiti by the target date.     

大连市2010年麻疹风疹疑似病例IgM抗体检测结果分析

目的:通过实验室麻疹、风疹IgM抗体检测结果,了解大连市2010年麻疹、风疹的流行特征,为促进免疫规划工作提供科学依据。方法:采用ELISA对2010年麻疹、风疹疑似病例血清标本进行IgM抗体检测;结果:全年共检测麻疹、风疹IgM抗体69份,麻疹IgM抗体阳性率为28.99%;风疹IgM抗体阳性率为43.48%;发病地区主要集中在流动人口频繁的城乡结合部,麻疹发病以5岁以内儿童为主,风疹以青少年居多;流行季节均主要为春季。结论:加强流动人口管理仍是今后防控的重点,同时继续加强计划免疫管理,开展查漏补种,做好疫情监测,预防暴发。     

舟山市健康人群麻疹、风疹、流行性腮腺炎和水痘抗体水平监测

目的：了解舟山市健康人群麻疹、风疹、腮腺炎和水痘的抗体水平,为制定相关免疫策略提供依据。方法选择舟山市健康人群,分为0～4、5～9、10～14、15～19、20～29、30～39、40～49、50~60岁8个年龄组,每个年龄组收集血清200份以上,使用ELISA法检测麻疹、风疹、腮腺炎和水痘IgG抗体,并计算其抗体阳性率和几何平均浓度（GMC）。结果麻疹和风疹的全人群抗体阳性率为分别为88.56%和81.61%,40～49岁组抗体阳性率最低,分别为80.75%和72.75%,不同年龄组间麻疹抗体阳性率﹑GMC 值和保护性抗体阳性率差异有统计学意义（χ2=42.696﹑F=41.341和χ2=179.160,P 均<0.01）;流行性腮腺炎全人群的抗体阳性率为88.77%,10～14岁组的抗体阳性率和 GMC 值最低71.18%和200.51 U/mL;水痘全人群的抗体阳性率为82.24%,0～4岁组抗体阳性率和GMC值最低,分别为52.51%和82.72 mIU/mL。结论麻疹和风疹的免疫水平总体较高,但中年人群的免疫水平偏低,10～14岁儿童流行性腮腺炎的免疫水平不高。水痘免疫水平明显低于其他三种疾病,建议加强对水痘疫苗的宣传。     

湛江市2006-2007年麻疹与风疹监测结果分析

目的 分析湛江市麻疹疑似病例的血清学实验室诊断符合率和风疹检测结果,完善麻疹监测网络实验室检测工作,为进一步提高麻疹、风疹的病例诊断提供依据.方法 应用ELISA法检测全市送检的血清样本中麻疹和风疹IgM抗体,对检测结果和病例资料进行分析.结果 实验室检测麻疹疑似病例血清样本747份,检出麻疹IgM抗体阳性502例,实验室诊断符合率为67.20%;在麻疹IgM抗体阴性血清样本中榆测风疹IgM抗体245份,阳性48例,阳性检出率为19.59%.麻疹发病高峰时间主要集中在3-7月,占病例总数的78.29%,风疹发病时间主要在4月和12月;麻疹发病年龄以0～9岁居多,占病例总数的73.31%,风疹发病年龄集中在15～24岁;麻疹、风疹病例的户籍分布均以本市户口为主,占病例总数的99%以上;麻疹男女比例为1.55:1,风疹男女比例为1.09:1;无免疫接种史或接种史不详的麻疹病例占95.02%,风疹病例占97.92%.结论 近两年,我市麻疹疫情上升较快,说明我市目前还没有形成足够保护易感人群的免疫屏障,全市计划免疫工作有待进一步加强;同时也应加强对风疹的控制.     

湖北省健康人群麻疹、风疹、腮腺炎人群免疫水平分析

目的:了解湖北省人群麻疹、风疹和腮腺炎抗体水平,制定免疫对策。方法:抽取咸宁市和黄石市两个地区部分健康人群,采集0岁～50岁健康人群标本共700份,使用ELISA法定量检测正常人血清中麻疹IgG、风疹IgG和腮腺炎IgG抗体水平。结果:麻疹、风疹和腮腺炎IgG抗体阳性率分别为87.14%、55.43%和61.86%。结论:抽取的湖北省两个地区健康人群风疹IgG和腮腺炎IgG抗体阳性率均比较低;控制麻疹重点人群为小于2岁年龄组;需要对风疹强化免疫以及对2岁以下儿童进行腮腺炎强化免疫。     

天津市麻疹风疹及流行性腮腺炎抗体水平分析

目的了解天津市健康人群麻疹、风疹、流行性腮腺炎抗体水平,评价疫苗接种需求。方法2007年3月采集0~57岁健康人群608人份血样品,用ELISA方法定量检测麻疹、风疹、流行性腮腺炎IgG抗体水平。运用直线相关分析抗体阳性率,保护率GMC与疾病发病率之间的关系,P0.05为差异有统计学意义。结果麻疹、风疹和流行性腮腺炎疫苗接种率分别为70.39%、16.78%和12.34%;抗体阳性率分别为91.78%,65.79%和73.52%;抗体几何平均浓度(GMC)分别为2 488.10 IU/L、200.4 IU/ml和759.91 U/ml。麻疹抗体阳性率,保护率与发病率存在明显相关关系(P0.01),而GMC与麻疹发病率没有显著性相关;风疹和流行性腮腺炎抗体阳性率、GMC与发病率无相关关系。结论本次调查显示2007年天津市麻疹人群抗体GMC总体保持在较高水平。风疹、流行性腮腺炎疫苗接种率和抗体水平较低,2剂次的麻腮风疫苗(MMR)纳入免疫规划既有助于消除麻疹,也有利于控制风疹和流行性腮腺炎。     

Development of measles vaccines in Japan

Studies on measles vaccine development started in 1950s in Japan. After 3-year studies on development of further attenuated live measles vaccines by Japan Measles Vaccine Research Commission, two kinds of vaccines of different strains were licensed for optional use in 1971. In 1978, periodical immunization against measles was started using BIKEN CAM-70 vaccine, Takeda Schwarz-FF8 vaccine and Kitasato AIK-C vaccine. Combined measles and rubella vaccines (MR vaccine) were licensed in 2005. Periodical immunization with MR vaccines of BIKEN and Takeda Pharmaceutical Co. Ltd. to eliminate measles together with rubella from Japan by 2012 was started for children 1- and 6 (5–7)-year of age in 2006.