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.     

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.     

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.     

Immune status of health care workers to measles virus: evaluation of protective titers in four measles IgG EIAs

BackgroundFollowing the recognition of a measles case in a hospital in The Netherlands, health care workers (HCW) from the premises were screened by a commercial enzyme immunoassay (EIA) for measles IgG to identify persons at risk for measles. At least 10% of the HCW were tested measles IgG-negative. As this was considered an unusually high proportion, we hypothesized suboptimal sensitivity of EIAs, especially in medical personnel that had vaccine-induced immunity rather than antibodies resulting from natural infection.ObjectivesTo determine (vaccine-induced) measles immunity in HCW, using different EIAs compared to the plaque reduction neutralization (PRN) test, the best surrogate marker for vaccine efficacy and immune protection.Study designSera from HCW were tested for measles IgG antibodies in three commercial EIAs, in a bead-based multiplex immunoassay (MIA) and in the PRN test, and evaluated against age and vaccination history of the HCW.ResultsOf the 154 HCW, born between 1960 and 1995, 153 (99.4%) had protective levels of measles antibodies (PRN > 120 mI U/ml). The three EIAs failed to detect any measles IgG antibodies in approximately 10% of the HCW, while this percentage was approximately 3% for the MIA. Negative IgG results rose to 19% for individuals born between 1975 and 1985, pointing to an age group largely representing vaccinated persons from the first measles vaccination period in The Netherlands.ConclusionThe results show limitations in the usefulness of current EIA assays for determining protective measles antibodies in persons with a vaccination history.     

Children vaccination coverage surveys: Impact of multiple sources of information and multiple contact attempts

BackgroundMonitoring vaccination coverage is an essential component of vaccination program evaluation. In Québec (Canada), children vaccination coverage surveys are conducted every two years since 2006. The objectives of this study were to evaluate the impact of supplementing data based on vaccination booklets with data from vaccine providers, on the final estimated vaccination coverage and to compare vaccination coverage between respondents to each survey contact attempt.MethodsData from six cross-sectional surveys were used, which included 3508 children aged 2 years. Parents were invited to transcribe the information available in their child’s vaccination booklet on the questionnaire received by mail. The survey included a maximum of 4 contact attempts to obtain a response. Data were completed among vaccine providers identified by parents. The main outcome was a complete vaccination status by 24 months of age.ResultsThe addition of data from vaccine providers to those present in vaccination booklets increased the proportion of children fully vaccinated from 5.5% to 23.7% depending on the survey year. The proportion of children fully vaccinated by 24 months of age estimated among respondents to contact 1 was only 2.1% higher than the estimates among all respondents.ConclusionsWithout validation among vaccine providers for children with missing doses according to vaccination booklets, results underestimated vaccination coverage in the target population. Conducting multiple contact attempts increased the response rate but had limited impact on the validity of estimates. It would be useful in future surveys to present the coverage obtain from respondents to each contact attempt.     

An animal component free medium that promotes the growth of various animal cell lines for the production of viral vaccines

IPT-AFM is a proprietary animal component free medium that was developed for rabies virus (strain LP 2061) production in Vero cells. In the present work, we demonstrated the versatility of this medium and its ability to sustain the growth of other cell lines and different virus strains. Here, three models were presented: Vero cells/rabies virus (strain LP 2061), MRC-5 cells/measles virus (strain AIK-C) and BHK-21 cells/rabies virus (strain PV-BHK21). The cell lines were first adapted to grow in IPT-AFM, by progressive reduction of the amount of serum in the culture medium. After their adaptation, BHK-21 cells grew in suspension by forming clumps, whereas MRC-5 cells remained adherent. Then, kinetics of cell growth were studied in agitated cultures for both cell lines. In addition, kinetics of virus replication were investigated.     

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.     

An outbreak of measles in Saitama City in 2007. What is the vaccination strategy to eliminate measles in Japan?

In the present study, to elucidate an outbreak of measles in Saitama City, Japan, we analyzed the data for all notified subjects with measles. According to an active surveillance program, a total of 464 subjects were notified in 2007. The clinical criteria for the diagnosis of measles were defined as at least 3 days of a generalized maculopapular rash; a fever of 38.0 degrees C or more; and cough, mucus, or pharyngitis. Two peaks according to age group were recognized: namely, children less than 2 years of age and adolescents from 15 to 19 years of age. The latter peak was associated with the period of time when the measles-mumps-rubella vaccine had become a social problem (40.9% of vaccinees and 41.6% of non-vaccinees in this group). Japan is said to be a developing country regarding its measles vaccination strategy. In addition, no national program against measles has yet been established. Continuous efforts to increase immunization coverage are needed to interrupt indigenous measles transmission. The Japanese Ministry of Health, Labor and Welfare should therefore plan and implement a nationwide program to eliminate measles in Japan.