Efficacy,immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.     

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.     

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.     

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.     

麻疹住院患者的临床分析及预防对策探讨(附462例报告)

目的 探讨住院麻疹患者的临床表现及流行新特点,为预防提供有针对性的参考对策.方法 将462例麻疹患者分为婴儿组(16d～＜1岁)、儿童组(1～17岁)、成人组(18～50岁),对其临床资料进行总结分析.结果 观察期间各月份均有麻疹住院病例,1～6月份398例,占86.1%,5月份最高,为104例,高发时间较以往向后延迟近1个月.流动人口患病多于常住人口,占68.2%.1岁以内婴儿占住院麻疹患者的49.6%,成人占28.1%,高发年龄段明显提前.麻疹集中好发年龄段,婴儿组为6～9个月龄,占64.6%;儿童组为1～5岁,占70.9%;成人组为18～39岁,占86.2%.8个月龄以上、符合麻疹计划免疫接种条件的349例中,接种疫苗者占12.0%,未接种者占88.0%;婴儿组中符合接种条件的116例中有17例接种疫苗,占14.7%;儿童组有接种史者占17.5%;成人组有明确疫苗接种史者仅占5.4%.有明确麻疹接触史者占19.0%.临床以上呼吸道卡他症状、充血性皮疹和发热为主要表现,婴儿组以肺炎、腹泻和白细胞升高多见,成人组则为一过性血尿和腹泻.结论 麻疹发病以流动人口为主,免疫接种率低.应加强流动儿童麻疹疫苗的接种或补种,其中婴儿免疫接种的起始月龄应适当提前.为保护易感人群,建议加强成人麻疹免疫抗体水平的监测,育龄妇女应列为强化免疫和监测的重点人群.     

The role of serum KL-6 measurement in common pediatric respiratory infections

KL-6 is a useful marker for interstitial pneumonia of various origins. However, the role of KL-6 in common pediatric respiratory infections is largely unknown. In order to determine whether the KL-6 level is elevated during respiratory infection, and whether KL-6 is a useful biomarker for the disease activity, we evaluated serum KL-6 levels in 132 children with various respiratory infections. KL-6 levels were significantly higher in patients with measles, influenza, or respiratory syncytial virus infection than in the control subjects. On the other hand, KL-6 levels in patients with bacterial infections such as mycoplasma, chlamydia, or pertussis were comparable to the control values. In patients with viral infections, high KL-6 levels, as defined by the mean plus 2 standard deviations of the control group, significantly correlated with low SpO₂ or days of O₂ administration, but did not correlate with C-reactive protein or white blood cell counts. These results indicate that measurement of serum KL-6 levels is helpful for the management of common pediatric respiratory infections.     

Effect of vaccine program on IgG antibody titers for measles,rubella, varicella,and mumps in young adults in Japan: Survey between 2018 and 2021

IntroductionImproved routine immunizations in Japan have led to a reduction in vaccine-preventable diseases. Due to changes in the vaccination program, current young adults received their second vaccination for measles and rubella at different times depending on their birth year, and most of them have not been vaccinated against varicella and mumps. This study investigated the effect of vaccine programs on the immunity of people in Japan.MethodsImmunoglobulin G antibody (IgG) titers against four viruses were determined by enzyme immunoassay in 795 students at a medical university. Titers for measles and rubella were compared according to the students’ birth dates (Group 1: April 2, 1990–April 1, 2000; Group 2: April 2, 2000–).ResultsThe titers of students that satisfied the standard IgG values against measles, rubella, varicella, and mumps were 24.3%, 56.9%, 87.4%, and 47.2%, respectively. Measles and rubella titers were lower in group 2 (estimated mean period from last vaccination, 7.0 years) than group 1 (13.5 years) (p = 0.023 measles, p = 0.037 rubella), indicating attenuation of titers over time. Varicella and mumps antibody prevalence indicated that these infections were endemic, whereas rates of negative titers were higher than those for measles and rubella.ConclusionsIgG titers against viruses were affected by vaccination programs. Declining titers after vaccination should be monitored when the diseases are almost eliminated and boosting is absent. Antibody testing is meaningful for recommending vaccinations and for surveillance of waning immunity. Continuous improvements of vaccination program should be considered to prevent and eliminate diseases.     

Characterizing the impact of spatial clustering of susceptibility for measles elimination

Measles elimination efforts are primarily focused on achieving and maintaining national vaccination coverage goals, based on estimates of the critical vaccination threshold (V_c): the proportion of the population that must be immune to prevent sustained epidemics. Traditionally, V_c estimates assume evenly mixing populations, an invalid assumption. If susceptible individuals preferentially contact one another, communities may remain vulnerable to epidemics even when vaccination coverage targets are met at the national level. Here we present a simple method to estimate V_c and the effective reproductive number, R, while accounting for spatial clustering of susceptibility. For measles, assuming R₀?=?15 and 95% population immunity, adjustment for high clustering of susceptibility increases R from 0.75 to 1.29, V_c from 93% to 96%, and outbreak probability after a single introduction from <1% to 23%. The impact of clustering remains minimal until vaccination coverage nears elimination levels. We illustrate our approach using Demographic and Health Survey data from Tanzania and show how non-vaccination clustering potentially contributed to continued endemic transmission of measles virus during the last two decades. Our approach demonstrates why high national vaccination coverage sometimes fails to achieve measles elimination, and that a shift from national to subnational focus is needed as countries approach elimination.