Affluence as a predictor of vaccine refusal and underimmunization in California private kindergartens

BackgroundNon-medical vaccine exemption rates in California private schools far exceed those of public schools, but little is known about specific factors which may be associated with high exemption rates in private schools.MethodsThe percent of personal-belief exemptions (PBEs) among California public and private kindergartens were computed for 2000–2001 to 2014–2015 academic years. For the 2014–2015 academic year, a random sample of private schools was selected to investigate associations between kindergarten characteristics (tuition amount, religious affiliation) and vaccine profile (non-medical vaccine exemptions, vaccine coverage).ResultsThe proportion of private kindergartens reporting 5% or more children with PBEs increased from 9% (2000–2001) to 34% (2013–2014), followed by a small decrease in 2014–2015 (31%). Overall, 93.7% (565/605) of kindergartens sampled in 2014–2015 had data available. Very high PBE levels (>20%) were seen among secular and non-Catholic, Christian kindergartens but not Roman Catholic, Jewish or Islamic kindergartens. However, the majority of schools at all tuition levels had fewer than 5% of children with a PBE. Kindergartens with an annual tuition of $10,000 or more were over twice as likely to have 20% or more children with PBEs than kindergartens with a lower tuition (p < .01). Additionally, the conditional admission proportions for kindergartens with tuitions of $10,000 or more were 39% compared to 22% for less expensive kindergartens (p < .01). Only about half of all private kindergartens had 95% coverage of the MMR (49%) and pertussis-containing vaccines (51%).ConclusionsSchool-entry vaccination requirements are critical to preventing outbreaks of vaccine preventable diseases in the US. Nonmedical exemptions increased between the 2000–2001 and 2014–2015 academic years and appear to be associated with affluence, raising social justice concerns.     

Parent perspectives on childhood vaccination: How to deal with vaccine hesitancy and refusal?

Background

The aims of the study are to evaluate attitudes about childhood vaccines and vaccine refusal or delay among parents and to assess the role played by the variables mapped as potential determinants to suggest strategies that could improve childhood vaccination rates.

麻疹疫苗强化免疫在消除麻疹中的作用

目的研究麻疹减毒活疫苗强化免疫效果,探讨预防控制措施,为消除麻疹提供依据。方法用描述性流行病学方法,分析2009年麻疹疫苗强化免疫活动开展情况,收集2009与2010年麻疹发病资料并对强化免疫接种效果进行分析。结果 2009年麻疹疫苗强化免疫活动适龄儿童接种报告接种率98.66%,调查接种率99.21%,各年龄组儿童接种率均在97%以上;2009年与2010年麻疹报告发病率分别为8.45/10万和0.53/10万,麻疹疫苗强化免疫前后麻疹发病率下降了93.73%;发病人群麻疹IgM抗体阳性率2009年80.00%,2010年28.57%。结论2009年麻疹强化免疫活动效果显著,应进一步研究麻疹免疫策略,以适应消除麻疹的需要。     

Potential impact of a maternal vaccine for RSV: A mathematical modelling study

Respiratory syncytial virus (RSV) is a major cause of respiratory morbidity and one of the main causes of hospitalisation in young children. While there is currently no licensed vaccine for RSV, a vaccine candidate for pregnant women is undergoing phase 3 trials. We developed a compartmental age-structured model for RSV transmission, validated using linked laboratory-confirmed RSV hospitalisation records for metropolitan Western Australia. We adapted the model to incorporate a maternal RSV vaccine, and estimated the expected reduction in RSV hospitalisations arising from such a program. The introduction of a vaccine was estimated to reduce RSV hospitalisations in Western Australia by 6–37% for 0–2 month old children, and 30–46% for 3–5 month old children, for a range of vaccine effectiveness levels. Our model shows that, provided a vaccine is demonstrated to extend protection against RSV disease beyond the first three months of life, a policy using a maternal RSV vaccine could be effective in reducing RSV hospitalisations in children up to six months of age, meeting the objective of a maternal vaccine in delaying an infant’s first RSV infection to an age at which severe disease is less likely.     

Routine and pulse vaccination for Lassa virus could reduce high levels of endemic disease: A mathematical modelling study

Lassa fever is an acute viral illness caused by Lassa virus (LASV), a rodent-borne pathogen. LASV is endemic to much of Sub-Saharan West Africa, where seasonal outbreaks cause significant morbidity and mortality. Increased global awareness of LASV has led to development of improved diagnostic tests, treatments and vaccines. As vaccine candidates are trialled, it is essential to assess the potential outcomes of introducing a LASV vaccination program in endemic regions. This study investigates the potential outcomes of routine and pulse vaccination strategies using a deterministic mathematical model that captures seasonal LASV transmission between rodents and humans. For plausible parameter values, we find that immunization of 40% of infants at 70% vaccine effectiveness achieves a population-level reduction in infectious case numbers of 30%, while coverage of 60% at 90% vaccine effectiveness achieves a 56% reduction. Similar reductions can be achieved more rapidly via population-wide pulse vaccination at 11% coverage (30% reduction at 70% effectiveness) or 23% coverage (56% reduction at 90% effectiveness) repeated every 10 years. Similar pulse vaccine doses delivered at reduced frequency, but increased coverage achieves a greater reduction in infectious cases. Findings around infant vaccination are sensitive to our assumption that immunity is life-long, while pulse-vaccination has only slightly reduced effect if immunity lasts 10–30 years. An effective LASV vaccination program would incorporate pulse vaccination in addition to routine childhood immunization to limit disease. Estimates of feasible vaccine coverage and effectiveness are needed to fully quantify the likely benefits of a vaccination program in LASV endemic regions.     

A survey on factors affecting acceptance of measles vaccine

The reasons for the low level of acceptance of measles vaccine were investigated through interviews with the mothers at the time of their children enrollment in the first year of attendance at several nursery schools in Milan city and its suburbs. Data were also collected on the natural disease.Only 192 (13.8%) of the 1386 children included in the study had already suffered natural measles and 45 of them before the age of 12 months. Of the total, 10% of the children had been vaccinated, more in the city of Milan than in the suburbs. Approximately one-half of the vaccinations had been administered by family doctors and the other half in Public Health facilities. Less than half of the vaccinations administered in the city of Milan proved to have been registered in Public Health Office records. The frequency of vaccinated children was significantly higher among mothers with higher levels of education than among those with lower levels of education.The reasons for the lack of vaccination most. frequently given by the mothers of the 1247 unvaccinated children were ignorance about the vaccine (38% of the mothers) and the belief that measles is an innocuous disease (36%). These were followed by fear of post-vaccinal reactions and advice against measles vaccine given, in most cases, by family doctors. The frequency of responses for each one of these reasons was significantly different in Milan with respect to the suburbs. This difference was also evident in the comparisons between mothers with higher levels of education with respect to mothers with low levels of education.Corresponding author.     

A systematic review of human-to-human transmission of measles vaccine virus

Measles is one of the most contagious human diseases. Administration of the live attenuated measles vaccine has substantially reduced childhood mortality and morbidity since its licensure in 1963. The live but attenuated form of the vaccine describes a virus poorly adapted to replicating in human tissue, but with a replication yield sufficient to elicit an immune response for long-term protection. Given the high transmissibility of the wild-type virus and that transmission of other live vaccine viruses has been documented, we conducted a systematic review to establish if there is any evidence of human-to-human transmission of the live attenuated measles vaccine virus. We reviewed 773 articles for genotypic confirmation of a vaccine virus transmitted from a recently vaccinated individual to a susceptible close contact. No evidence of human-to-human transmission of the measles vaccine virus has been reported amongst the thousands of clinical samples genotyped during outbreaks or endemic transmission and individual case studies worldwide.     

Effect of early measles vaccination on long-term protection: A systematic review

BackgroundIn North America, the first dose of a measles-containing vaccine (MCV1) is administered at ≥12 months of age. However, MCV1 may be given to infants <12 months living in highly endemic areas or traveling to these areas. Although an early dose of MCV1 leads to immediate protection, it remains unclear how this impacts long-term immunity.MethodsThis systematic review and meta-analysis evaluates the impact of MCV1 given at <12 months vs. ≥12 months of age on long-term immunogenicity and vaccine effectiveness, with long-term defined as at least one-year post-vaccination. PubMed, EMBASE, Global Health, Web of Science and Scopus were searched on October 31st, 2019. Studies were included if they included a cohort of infants vaccinated <12 months of age and evaluated long-term immunogenicity, vaccine efficacy, or effectiveness.ResultsA total of 51 texts were identified: 23 reported outcomes related to vaccine effectiveness and 30 to immunogenicity. Infants vaccinated with MCV1 < 12 months of age showed an overall higher risk of measles compared to ≥12 months of age (RR = 3.16, 95% CI: 2.00, 5.01; OR = 2.46, 95% CI: 1.40, 4.32). Risk of measles decreased with increasing age at first vaccination, with those vaccinated with one dose ≥15 months at a lesser risk compared to 12–14 months or <12 months. Measles seroconversion and seropositivity was not affected by age at first vaccination, but antibody levels were significantly lower in the MCV1 < 12-month group (MD = −0.40, 95% CI: −0.71, −0.09).ConclusionLong-term measles seroconversion and seropositivity did not appear to be affected by age at MCV1, while vaccine effectiveness decreased with younger age. There was not enough evidence to look at the effect of age at MCV1 on immune blunting.     

Economic analysis of measles elimination program in the Republic of Korea, 2001: A cost benefit analysis study

Background

In this study, we modeled the cost benefit analysis for three different measles vaccination strategies based upon three different measles-containing vaccines in Korea, 2001. We employed an economic analysis model using vaccination coverage data and population-based measles surveillance data, along with available estimates of the costs for the different strategies. In addition, we have included analysis on benefit of reduction of complication by mumps and rubella.

Methods

We evaluated four different strategies: strategy 1, keep-up program with a second dose measles-mumps-rubella (MMR) vaccine at 4–6 years without catch-up campaign; strategy 2, additional catch-up campaign with measles (M) vaccine; strategy 3, catch-up campaign with measles-rubella (MR) vaccine; and strategy 4, catch-up campaign with MMR vaccine. The cost of vaccination included cost for vaccines, vaccination practices and other administrative expenses. The direct benefit of estimated using data from National Health Insurance Company, a government-operated system that reimburses all medical costs spent on designated illness in Korea.

Results

With the routine one-dose MMR vaccination program, we estimated a baseline of 178,560 measles cases over the 20 years; when the catch-up campaign with M, MR or MMR vaccines was conducted, we estimated the measles cases would decrease to 5936 cases. Among all strategies, the two-dose MMR keep-up program with MR catch-up campaign showed the highest benefit-cost ratio of 1.27 with a net benefit of 51.6 billion KRW.

Conclusion

Across different vaccination strategies, our finding suggest that MR catch-up campaign in conjunction with two-dose MMR keep-up program was the most appropriate option in terms of economic costs and public health effects associated with measles elimination strategy in Korea.     

安徽省2015-2016年麻疹发病影响因素病例对照研究

目的 探讨安徽省≤7月龄婴儿、8月龄~14岁儿童、≥15岁成人麻疹发病影响因素,为制定麻疹干预策略提供科学依据。方法 选择中国疾病预防控制信息系统中实验室确诊的麻疹病例,采用成组对照的方法进行调查。结果 三个年龄组各232名病例和对照纳入研究,多因素分析结果显示,≤7月龄婴儿组危险因素为6~7月龄（OR=5.255,95% CI：3.092~8.931）、住在城乡结合部（OR=3.035,95% CI：1.236~7.454）、早产（OR=14.896,95% CI：3.756~59.074）,保护因素为母乳喂养（OR=0.297,95% CI：0.153~0.574）和有兄弟姐妹（OR=0.464,95% CI：0.276~0.781）。8月龄~14岁儿童组危险因素为住在城乡结合部（OR=3.347,95%CI：1.365~8.204）、早产（OR=3.171,95% CI：1.185~8.487）,保护因素为母乳喂养（OR=0.313,95% CI：0.175~0.558）。≥15岁成人组危险因素为流动人口（OR=3.900,95% CI：1.633~9.311）、居住城乡结合部（OR=5.564,95% CI：2.485~12.459）,保护因素为与＜15岁儿童同住（OR=0.383,95% CI：0.216~0.682）。其他如男性、祖父母看护、外出史和医院暴露史等均是危险因素（均有P<0.05）,有接种证、含麻疹成分疫苗免疫史等均是保护因素。结论 根据本研究结果提议应确保MCV两剂次95%接种率和首剂次及时接种,控制院内感染的发生,提倡优生优育、母乳喂养,在麻疹高发季节尽量避免去人多拥挤的地方。     

A model to evaluate mass vaccination against pneumococcus as a countermeasure against pandemic influenza

A mathematical model has been developed for the purpose of evaluating vaccination against pneumococcus as a countermeasure against pandemic influenza. As the characteristics of a future pandemic cannot be known in advance, three distinct pandemic scenarios were considered, corresponding to a 1918-like pandemic, a 1957/1968-like pandemic and a 2009-like pandemic.Model estimates for each of these pandemic scenarios are presented for two options of vaccination programme; universal vaccination of the entire UK population and vaccination only of those people considered to be at heightened risk of developing influenza complications. We find that the benefits of each option (in terms of estimated number of deaths and hospital admissions avoided and the courses of antibiotics saved) are high in a 1918-like pandemic and very small in a 2009-like pandemic. Given that the decision regarding deployment of the counter measure would occur prior to knowledge of the flu-strain characteristics being available, we also present the weighted average of the outcomes from the three pandemic scenarios. Based on the historical occurrence of pandemics over the last 100 years, the weighted average of outcomes is an estimated 1400 deaths prevented by the universal vaccination option and 400 deaths saved by the targeted vaccination option (at a cost of approximately 400 million and 50 million courses of vaccine respectively).Finally, the longer term implications of using PPV as a countermeasure against pandemic influenza have been considered by estimating the expected number of courses of vaccine bought and the expected number of deaths and hospital admissions prevented over time under each policy.     

An economic evaluation of the current measles vaccination program: A case study in Zhejiang Province,east China

ObjectiveTo evaluate the economic impact of the current measles vaccination program in Zhejiang Province, east China.MethodsA decision tree-Markov model with parameters from published literatures, government documents and surveys was developed and used to simulate over 40 years of a birth cohort in Zhejiang Province during the year 2014. The expected cost and effectiveness of the current measles vaccination program was compared against no vaccination. Costs were assessed from the payer's perspective. Benefits were defined as savings on the direct cost of measles treatment, and the effectiveness was measured according to the number of measles cases and deaths averted. The net present value (NPV), benefit-cost ratio (BCR) and incremental cost-effectiveness ratio (ICER) were also calculated. A threshold for cost-effectiveness of less than 3 times the Gross Domestic Product (GDP) per capita was used. One-way sensitivity analysis was performed to assess parameter uncertainties.ResultsThe total vaccination cost was estimated to be $2.52 million. The BCR of the current measles program was found to be 6.06 with a NPV of $73.38 million. It was also calculated that a total of 195,165 measles cases and 191 measles-related deaths would be prevented by vaccination. The ICER was approximately $12.91 per case averted and $13,213.43 per death averted, respectively, which was cost-effective. The models were proven to be robust.ConclusionsThe current measles vaccination program appeared to be cost-effective and to offer substantial benefits. The results of this analysis sought to contribute to the justification of future investments to achieve the goal of measles elimination.     

The recombinant globular head domain of the measles virus hemagglutinin protein as a subunit vaccine against measles

Despite the availability of live attenuated measles virus (MV) vaccines, a large number of measles-associated deaths occur among infants in developing countries. The development of a measles subunit vaccine may circumvent the limitations associated with the current live attenuated vaccines and eventually contribute to global measles eradication. Therefore, the goal of this study was to test the feasibility of producing the recombinant globular head domain of the MV hemagglutinin (H) protein by stably transfected human cells and to examine the ability of this recombinant protein to elicit MV-specific immune responses. The recombinant protein was purified from the culture supernatant of stably transfected HEK293T cells secreting a tagged version of the protein. Two subcutaneous immunizations with the purified recombinant protein alone resulted in the production of MV-specific serum IgG and neutralizing antibodies in mice. Formulation of the protein with adjuvants (polyphosphazene or alum) further enhanced the humoral immune response and in addition resulted in the induction of cell-mediated immunity as measured by the production of MV H-specific interferon gamma (IFN-γ) and interleukin 5 (IL-5) by in vitro re-stimulated splenocytes. Furthermore, the inclusion of polyphosphazene into the vaccine formulation induced a mixed Th1/Th2-type immune response. In addition, the purified recombinant protein retained its immunogenicity even after storage at 37°C for 2 weeks.     

Estimating the cost of cholera-vaccine delivery from the societal point of view: A case of introduction of cholera vaccine in Bangladesh

Cholera is a major global public health problem that causes both epidemic and endemic disease. The World Health Organization recommends oral cholera vaccines as a public health tool in addition to traditional prevention practices and treatments in both epidemic and endemic settings. In many developing countries like Bangladesh, the major issue concerns the affordability of this vaccine. In February 2011, a feasibility study entitled, “Introduction of Cholera Vaccine in Bangladesh (ICVB)”, was conducted for a vaccination campaign using inactivated whole-cell cholera vaccine (Shanchol) in a high risk area of Mirpur, Dhaka. Empirical data obtained from this trial was used to determine the vaccination cost for a fully immunized person from the societal perspective. A total of 123,661 people were fully vaccinated receiving two doses of the vaccine, while 18,178 people received one dose of the same vaccine. The total cost for vaccine delivery was US$ 492,238 giving a total vaccination cost per fully-vaccinated individual of US$ 3.98. The purchase cost of the vaccine accounted for 58% of the overall cost of vaccination. Attempts to reduce the per-dose cost of the vaccine are likely to have a large impact on the cost of similar vaccination campaigns in the future.     

Review of mathematical models of HSV-2 vaccination: Implications for vaccine development

Development of a vaccine against herpes simplex virus type 2 (HSV-2), a life-long sexually-transmitted infection (STI), would be a major step forward in improving global sexual and reproductive health. In this review, we identified published literature of dynamic mathematical models assessing the impact of either prophylactic or therapeutic HSV-2 vaccination at the population level. We compared each study’s model structure and assumptions as well as predicted vaccination impact. We examined possible causes of heterogeneity across model predictions, key gaps, and the implications of these findings for future modelling efforts. Only eight modelling studies have assessed the potential public health impact of HSV-2 vaccination, with the majority focusing on impact of prophylactic vaccines. The studies showed that even an imperfect prophylactic HSV-2 vaccine could have an important public health impact on HSV-2 incidence, and could also impact HIV indirectly in high HIV prevalence settings. Therapeutic vaccines also may provide public health benefits, though they have been explored less extensively. However, there was substantial variation in predicted population-level impact for both types of vaccine, reflecting differences in assumptions between model scenarios. Importantly, many models did not account for heterogeneity in infection rates such as by age, sex and sexual activity. Future modelling work to inform decisions on HSV vaccine development and implementation should consider cost-effectiveness, account for additional HSV-2 sequelae such as neonatal transmission, and model greater heterogeneity in infection rates between individuals, more realistic vaccine deployment, and more thorough sensitivity and uncertainty analyses.     

A global perspective of vaccination of healthcare personnel against measles: Systematic review

Measles transmission has been well documented in healthcare facilities. Healthcare personnel who are unvaccinated and who lack other evidence of measles immunity put themselves and their patients at risk for measles. We conducted a systematic literature review of measles vaccination policies and their implementation in healthcare personnel, measles seroprevalence among healthcare personnel, measles transmission and disease burden in healthcare settings, and impact/costs incurred by healthcare facilities for healthcare-associated measles transmission. Five database searches yielded 135 relevant articles; 47 additional articles were found through cross-referencing. The risk of acquiring measles is estimated to be 2 to 19 times higher for susceptible healthcare personnel than for the general population. Fifty-three articles published worldwide during 1989–2013 reported measles transmission from patients to healthcare personnel; many of the healthcare personnel were unvaccinated or had unknown vaccination status. Eighteen articles published worldwide during 1982–2013 described examples of transmission from healthcare personnel to patients or to other healthcare personnel. Half of European countries have no measles vaccine policies for healthcare personnel. There is no global policy recommendation for the vaccination of healthcare personnel against measles. Even in countries such as the United States or Finland that have national policies, the recommendations are not uniformly implemented in healthcare facilities. Measles serosusceptibility in healthcare personnel varied widely across studies (median 6.5%, range 0–46%) but was consistently higher among younger healthcare personnel. Deficiencies in documentation of two doses of measles vaccination or other evidence of immunity among healthcare personnel presents challenges in responding to measles exposures in healthcare settings. Evaluating and containing exposures and outbreaks in healthcare settings can be disruptive and costly. Establishing policies for measles vaccination for healthcare personnel is an important strategy towards achieving measles elimination and should be a high priority for global policy setting groups, governments, and hospitals.     

Public opponents of vaccination: a case study

Opposition to mass childhood vaccination is a world-wide phenomenon, particularly in industrialised countries. Unfounded claims about vaccination are perpetuated by parental lobby groups and individual spokespeople, some of whom have a medical or scientific background. This article focuses on one such spokesperson who has achieved particular notoriety. Dr. Viera Scheibner is a retired micropalaeontologist, without any formal training in health-related sciences, who tours the world claiming that vaccines are ineffective and dangerous and lead to a host of ills such as cancer and asthma. Professionals in public health or the clinical arena are from time to time called upon to publicly respond to her, or similar, claims disseminated during tours of Europe, North America or Australasia and in books and articles. Health professionals have expressed at how such spokespersons misrepresent the evidence on vaccine safety, resulting in the potential to undermine public confidence in immunisation. Media coverage, or proposed coverage, particularly of her more extreme claims, often makes health professionals engaged in immunisation feel obliged to respond. This paper describes Viera Scheibner’s approach, which follows a repetitious path and is representative of that taken by other public opponents of immunisation. We conclude by suggesting how health professionals might respond in the public arena.     

Modelling the relative benefits of using the measles vaccine outside cold chain for outbreak response

IntroductionRapid outbreak response vaccination is a strategy for measles control and elimination. Measles vaccines must be stored and transported within a specified temperature range, but this can present significant challenges when targeting remote populations. Measles vaccine licensure for delivery outside cold chain (OCC) could provide more vaccine transport/storage space without ice packs, and a solution to shorten response times. However, due to vaccine safety and wastage considerations, the OCC strategy will require other operational changes, potentially including the use of 1-dose (monodose) instead of 10-dose vials, requiring larger transport/storage equipment currently achieved with 10-dose vials. These trade-offs require quantitative comparisons of vaccine delivery options to evaluate their relative benefits.MethodsWe developed a modelling framework combining elements of the vaccine supply chain - cold chain, vial, team, and transport equipment types - with a measles transmission dynamics model to compare vaccine delivery options. We compared 10 strategies resulting from combinations of the vaccine supply elements and grouped into three main classes: OCC, partial cold chain (PCC), and full cold chain (FCC). For each strategy, we explored a campaign with 20 teams sequentially targeting 5 locations with 100,000 individuals each. We characterised the time needed to freeze ice packs and complete the campaign (campaign duration), vaccination coverage, and cases averted, assuming a fixed pre-deployment delay before campaign commencement. We performed sensitivity analyses of the pre-deployment delay, population sizes, and two team allocation schemes.ResultsThe OCC, PCC, and FCC strategies achieve campaign durations of 50, 51, and 52 days, respectively. Nine of the ten strategies can achieve a vaccination coverage of 80%, and OCC averts the most cases.DiscussionThe OCC strategy, therefore, presents improved operational and epidemiological outcomes relative to current practice and the other options considered.