Is annual vaccination best? A modelling study of influenza vaccination strategies in children

IntroductionAnnual vaccination of children against influenza is a key component of vaccination programs in many countries. However, past infection and vaccination may affect an individual’s susceptibility to infection. Little research has evaluated whether annual vaccination is the best strategy. Using the United Kingdom as our motivating example, we developed a framework to assess the impact of different childhood vaccination strategies, specifically annual and biennial (every other year), on attack rate and expected number of infections.Methods and findingsWe present a multi-annual, individual-based, stochastic, force of infection model that accounts for individual exposure histories and disease/vaccine dynamics influencing susceptibility. We simulate birth cohorts that experience yearly influenza epidemics and follow them until age 18 to determine attack rates and the number of infections during childhood. We perform simulations under baseline conditions, with an assumed vaccination coverage of 44%, to compare annual vaccination to no and biennial vaccination. We relax our baseline assumptions to explore how our model assumptions impact vaccination program performance.At baseline, we observed less than half the number of infections between the ages 2 and 10 under annual vaccination in children who had been vaccinated at least half the time compared to no vaccination. When averaged over all ages 0–18, the number of infections under annual vaccination was 2.07 (2.06, 2.08) compared to 2.63 (2.62, 2.64) under no vaccination, and 2.38 (2.37, 2.40) under biennial vaccination. When we introduced a penalty for repeated exposures, we observed a decrease in the difference in infections between the vaccination strategies. Specifically, the difference in childhood infections under biennial compared to annual vaccination decreased from 0.31 to 0.04 as exposure penalty increased.ConclusionOur results indicate that while annual vaccination averts more childhood infections than biennial vaccination, this difference is small. Our work confirms the value of annual vaccination in children, even with modest vaccination coverage, but also shows that similar benefits of vaccination may be obtained by implementing a biennial vaccination program.Author summaryMany countries include annual vaccination of children against influenza in their vaccination programs. In the United Kingdom (UK), annual vaccination of children aged of 2 to 10 against influenza is recommended. However, little research has evaluated whether annual vaccination is the best strategy, while accounting for how past infection and vaccination may affect an individual’s susceptibility to infection in the current influenza season. Prior work has suggested that there may be a negative effect of repeated vaccination. In this work we developed a stochastic, individual-based model to assess the impact of repeated vaccination strategies on childhood infections. Specifically, we first compare annual vaccination to no vaccination and then annual vaccination to biennial (every other year) vaccination. We use the UK as our motivating example. We found that an annual vaccination strategy resulted in the fewest childhood infections, followed by biennial vaccination. The difference in number of childhood infections between the different vaccination strategies decreased when we introduced a penalty for repeated exposures. Our work confirms the value of annual vaccination in children, but also shows that similar benefits of vaccination can be obtained by implementing a biennial vaccination program, particularly when there is a negative effect of repeated vaccinations.     

Peptide vaccination is superior to genetic vaccination using a recombineered bacteriophage λ subunit vaccine

Genetic immunization holds promise as a vaccination method, but has so far proven ineffective in large primate and human trials. Herein, we examined the relative merits of genetic immunization and peptide immunization using bacteriophage λ. Bacteriophage λ has proven effective in immune challenge models using both immunization methods, but there has never been a direct comparison of efficacy and of the quality of immune response. In the current study, this vector was produced using a combination of cis and trans phage display. When antibody titers were measured from immunized animals together with IL-2, IL-4 and IFNγ production from splenocytes in vitro, we found that proteins displayed on λ were superior at eliciting an immune response in comparison to genetic immunization with λ. We also found that the antibodies produced in response to immunization with λ displayed proteins bound more epitopes than those produced in response to genetic immunization. Finally, the general immune response to λ inoculation, whether peptide or genetic, was dominated by a Th1 response, as determined by IFNγ and IL-4 concentration, or by a higher concentration of IgG2a antibodies.     

Is vaccination coverage a good indicator of age-appropriate vaccination? A prospective study from Uganda

Background

Timely vaccination is important to protect children from common infectious diseases. We assessed vaccination timeliness and vaccination coverage as well as coverage of vitamin A supplementation in a Ugandan setting.

Methods and findings

This study used vaccination information gathered during a cluster-randomized trial promoting exclusive breastfeeding in Eastern Uganda between 2006 and 2008 (ClinicalTrials.gov no. NCT00397150). Five visits were carried out from birth up to 2 years of age (median follow-up time 1.5 years), and 765 children were included in the analysis. We used Kaplan-Meier time-to-event analysis to describe vaccination coverage and timeliness. Vaccination coverage at the end of follow-up was above 90% for all vaccines assessed individually that were part of the Expanded Program on Immunization (EPI), except for the measles vaccine which had 80% coverage (95%CI 76-83). In total, 75% (95%CI 71-79) had received all the recommended vaccines at the end of follow-up. Timely vaccination according to the recommendations of the Ugandan EPI was less common, ranging from 56% for the measles vaccine (95%CI 54-57) to 89% for the Bacillus Calmette-Guérin (BCG) vaccine (95%CI 86-91). Only 18% of the children received all vaccines within the recommended time ranges (95%CI 15-22). The children of mothers with higher education had more timely vaccination. The coverage for vitamin A supplementation at end of follow-up was 84% (95%CI 81-87).

Conclusions

Vaccination coverage was reasonably high, but often not timely. Many children were unprotected for several months despite being vaccinated at the end of follow-up. There is a need for continued efforts to optimise vaccination timeliness.     

Is viral status needed before vaccination?

Human Papillomavirus (HPV) testing prior to HPV vaccination is not recommended unless HPV tests are part of the established local routines for cervical cancer screening. The reasoning is based upon the very low frequency of women who, at the time of vaccination, would show markers of prior/current exposure (HPV DNA or serological tests) to the HPV types included in the vaccine. Thus at least one thousand women would need to be screened to find one that is HPV 16 and 18 DNA positive. The increase in cost and the other barriers afforded by a prior to vaccination test requirement would result in a lower coverage, the key indicator of a successful vaccination program.     

Did the temporary suspension of Vaxzveria vaccinations influence COVID-19 vaccination intentions,vaccination perceptions and trust in the vaccination campaign? A repeated survey study in the Netherlands

In spring 2021, several countries, among which the Netherlands, suspended vaccinations against COVID-19 with the Vaxzevria vaccine from AstraZeneca after reports of rare but severe adverse events. This study investigates the influence of this suspension on the Dutch public’s perceptions of COVID-19 vaccinations, trust in the government’s vaccination campaign, and COVID-19 vaccination intentions. We conducted two surveys in a population of general Dutch public (18 + ), one shortly before the pause of AstraZeneca vaccinations and one shortly thereafter (N eligible for analysis = 2628). Our results suggest no changes in perceptions nor intentions regarding the COVID-19 vaccines in general but do suggest a decline in trust in the government’s vaccination campaign. In addition, after the suspension, perceptions of the AstraZeneca vaccines were more negative in comparison to those of COVID-19 vaccinations in general. AstraZeneca vaccination intentions were also considerably lower. These results stress the need to adapt vaccination policies to anticipated public perceptions and responses following a vaccine safety scare, as well as the importance of informing citizens about the possibility of very rare adverse events prior to the introduction of novel vaccines.     

Adolescents’ attitudes to the COVID-19 vaccination

Vaccines against COVID-19 are now available for adolescents in Hong Kong but vaccine hesitancy is a major barrier to herd immunity. This survey study explores Hong Kong adolescents’ attitudes towards the COVID-19 vaccination. 2609 adolescents from across Hong Kong completed an online survey focused on the intent to vaccinate and the reasons for their choice. 39% of adolescents intended to take the COVID-19 vaccination and significant factors for this decision include: having at least one parent vaccinated, knowing somebody diagnosed with COVID-19 and receiving the influenza vaccine. Adolescents’ major concerns were either the safety and efficacy of the vaccine or the risk of infection. This study has proved that even in adolescents the vaccine hesitancy model is prominent with adolescents’ intentions highly related to confidence in the vaccine and perception of disease risk. Future interventions should target these specific concerns to ensure adolescents are well educated to overcome vaccine hesitancy.     

Increasing vaccination coverage: The school entry vaccination record check program in Guizhou Province China, 2003–2018

BackgroundGuizhou Province of China implements a vaccination program specifying that children’s vaccination records are to be checked upon entry to kindergarten and primary school; children missing one or more recommended vaccinations are to be offered the missed vaccinations; school-level vaccination coverage levels are assessed at the time of school enrollment and six months later to monitor compliance rates.MethodsWe obtained the number of doses of each vaccine in the national immunization schedule that were administered before and six months after kindergarten and school enrollment and reported to Guizhou Province during 2004 through 2018. We determined temporal trends in coverage of the second dose of measles-containing vaccine (MCV2) and other vaccines, incidence of measles, and number of school-based measles outbreaks.ResultsMCV2 coverage at kindergarten entry increased from 53% in 2004 to 98% in 2018. Among children missing one or more vaccinations, the six-month catch-up rate of MCV2 increased from 80% in 2004 to 99% in 2018. Among primary school children, coverage of MCV2 and other recommended vaccines had similar increases. The annual incidence of measles among Guizhou’s total population declined from 280 per million in 2003 to 0.3 per million in 2018. There have been no measles outbreaks in kindergartens or schools since 2015.ConclusionsChecking vaccination record at kindergartens and primary schools and providing necessary catch-up vaccination was associated with increased coverage of measles and other vaccines, lower incidence of measles, and an apparent end to school-based measles outbreaks. Guizhou’s experience of checking vaccination records at school enrollment led to implementation of this strategy in other provinces. In 2019, the kindergarten and school entry vaccination record check program was incorporated into China’s national vaccine law.     

Are vaccination sites in Bangladesh scale efficient?

OBJECTIVES: The overall aim of this study is to discern whether and to what degree vaccination sites exhibit constant returns to scale. METHODS: Data Envelopment Analysis is used to compare all the facilities in the sample in terms of input costs used to produce multiple outputs. The application considers the Expanded Program on Immunization (EPI), which operated in Dhaka City, Bangladesh, during 1999. RESULTS: A preponderance of EPI sites were determined to be operating at increasing returns to scale. CONCLUSIONS: Our findings question the applicability of cost-effectiveness analyses that assume constant returns to scale.     

Is vaccination against transmissible spongiform encephalopathy feasible?

Prion diseases are a unique category of illness, affecting both animals and humans, where the underlying pathogenesis is related to a conformation change of the cellular form of a normal, self-protein called a prion protein (PrP(c) [C for cellular]) to a pathological and infectious conformation known as scrapie form (PrPsc [Sc for scrapie]). Currently, all prion diseases are without effective treatment and are universally fatal. The emergence of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease has highlighted the need to develop possible therapies. In Alzheimer's disease (AD), which has similarities to prion diseases, both passive and active immunisation have been shown to be highly effective at preventing disease and cognitive deficits in model animals. In a human trial of active vaccination in AD, despite indications of cognitive benefits in patients with an adequate humoral response, 6% of patients developed significant complications related to excessive cell-mediated immunity. This experience highlights that immunotherapies designed to be directed against a self-antigen have to finely balance an effective humoral immune response with potential autoimmune toxicity. Many prion diseases have the gut as a portal of infectious agent entry. This makes mucosal immunisation a potentially very attractive method to partially or completely prevent prion entry across the gut barrier and to also produce a modulated immune response that is unlikely to be associated with any toxicity. The authors' recent results using an attenuated Salmonella vaccine strain expressing the prion protein show that mucosal vaccination can partially protect against prion infection from a peripheral source, suggesting the feasibility of this approach.     

Does influenza vaccination exacerbate asthma in children?

BACKGROUND: The risks of influenza vaccination in asthmatic children are still being discussed. Especially, the risk that influenza vaccination may exacerbate asthma is an issue in this debate. METHODS: We conducted a randomised double-blind placebo-controlled trial in 696 children 6-18 years of age with asthma recruited in general practice during two influenza seasons, 1999-2000 and 2000-2001. Children participated for only one season. During the first week after vaccination, participants recorded local, influenza like and asthma symptoms as well as use of medication, health care use and absenteeism. RESULTS: Except for cough during the day in the first season, favouring placebo, there were no differences indicating that vaccination exacerbates asthma. CONCLUSIONS: Influenza vaccination does not seem to exacerbate asthma.     

Pharmacies versus doctors’ offices for adolescent vaccination

PurposeWe sought to understand the relative advantage of pharmacies compared to doctors’ offices for delivering HPV vaccination to adolescents.MethodsParticipants were a national sample of 1500 U.S. parents of adolescents ages 11–17 recruited in 2014–15. In an online survey, items informed by Diffusion of Innovation Theory assessed parents’ perceptions of the relative advantages of HPV vaccine delivery in pharmacies and doctors’ offices.Principle findingsMany parents believed doctor’s offices offered a better health care environment than pharmacies, with more privacy (77%) and a safer place for vaccination (70%). However, many parents also believed pharmacies were more accessible than doctors’ offices, requiring less time for vaccinations (71%) and offering more convenient hours (59%). Parents were more willing to get their children HPV vaccine from pharmacists if they indicated more relative advantages in vaccine delivery in pharmacies (β = .29; p < .001) and believed patient accessibility more important than health care environment (β = .20; p < .001).ConclusionsTo be more appealing to parents as HPV vaccine providers, pharmacy providers within community and hospital settings should build on their relative advantage with respect to accessibility and enhance their appeal of their healthcare environment.     

Effectiveness of subunit influenza vaccination in the 2014–2015 season and residual effect of split vaccination in previous seasons

BackgroundIn Navarra, Spain, subunit vaccine was first used in the 2014–2015 season, whereas trivalent split-virion influenza vaccines had been used in previous seasons. We estimate the effectiveness of the subunit vaccine in the current season and split vaccine in the two previous seasons against laboratory-confirmed influenza in the 2014–2015 season.MethodsPatients with influenza-like illness hospitalized or attended by sentinel general practitioners were swabbed for influenza testing. The previous and current vaccine status of laboratory-confirmed cases was compared to test-negative controls.ResultsAmong 1213 patients tested, 619 (51%) were confirmed for influenza virus: 52% influenza A(H3N2), 46% influenza B, and 2% A(H1N1)pdm09. The overall effectiveness for subunit vaccination in the current season was 19% (95% confidence interval [CI]: −13 to 42), 2% (95%CI: −47 to 35) against influenza A(H3N2) and 32% (95%CI: −4 to 56) against influenza B. The effectiveness against any influenza was 67% (95%CI: 17–87) for 2012–2013 and 2013–2014 vaccination only, 42% (95%CI: −31 to 74) for 2014–2015 vaccination only, and 38% (95%CI: 8–58) for vaccination in the 2012–2013, 2013–2014 and 2014–2015 seasons. The same estimates against influenza A(H3N2) were 47% (95%CI: −60 to 82), −54% (95%CI: −274 to 37) and 28% (95%CI: −17 to 56), and against influenza B were 82% (95%CI: 19–96), 93% (95%CI: 45–99) and 43% (95%CI: 5–66), respectively.ConclusionThese results suggest a considerable residual protection of split vaccination in previous seasons, low overall effectiveness of current season subunit vaccination, and possible interference between current subunit and previous split vaccines.     

Cost–benefit of the introduction of new strategies for vaccination against pertussis in Spain: Cocooning and pregnant vaccination strategies

BackgroundPertussis remains a public health problem in countries with high vaccination coverage. Classic vaccination approaches have failed to effectively control the infection. The incidence of pertussis hospitalizations in infants is high, especially in those younger than 3 months who are in high risk of a severe disease and death. Additional strategies are recommended for short-term protection of this vulnerable population. In this study, we estimated the impact of 2 strategies for pertussis prevention in infants younger than 1 year of age—a cocoon vaccination strategy and the vaccination of pregnant women (VPW)—and the cost–benefit of these approaches relative to the current vaccination policy in Spain.MethodsA cost–benefit analysis was conducted from the perspective of the publically-funded Spanish healthcare system, based on the yearly number of hospitalizations during the period of 2009 to 2011. We calculated the absolute risk reduction, the number of parents that would need to be vaccinated to prevent 1 hospitalization or death in infants <1 year, and the net benefit-to-cost ratio of each strategy.ResultsFrom 2009 to 2011, the incidence of pertussis in Spain was 153.44 hospitalizations per 100,000 infants <1 year. The absolute risk reduction for hospitalization would be 42.1/100,000 with cocooning and 75.2/100,000 with VPW. The number of parents needed to vaccinate with the cocoon strategy to prevent 1 pertussis hospitalization would be 4752 and to prevent 1 death, more than 900,000. With VPW, 1331 pregnant women would have to be vaccinated to prevent 1 hospitalization and 200,000 to prevent 1 death. The benefit-to-cost ratio was 0.04 for cocooning and 0.15 for VPW.     

HPV vaccination: Are we initiating too late?

Background

Human papillomavirus (HPV) vaccination is recommended in early adolescence. While limited data suggest that patients frequently delay initiation of the three-dose series, age-based variability in initiation of HPV vaccination and its clinical relevance are not well described. Thus, this study aims to characterize HPV vaccination delay among adolescent and young adult females.

Methods

This retrospective cohort study examined age at HPV vaccination initiation and missed opportunities for receipt of the first vaccine dose (HPV1) among 11–26 year-old females (n = 22,900) receiving care at 16 urban academically-affiliated ambulatory care clinics between 2007 and 2011. Predictors of timely vaccination and post-licensure trends in age at HPV1 receipt were assessed using multivariable logistic regression and a generalized linear mixed model, respectively. Chlamydia trachomatis and Papanicolaou screening before HPV vaccination initiation, as markers of prior sexual experience and associated morbidity, were examined in a subcohort of subjects (n = 15,049).

Results

The proportion of 11–12 year-olds who initiated HPV vaccination increased over time (44.4% [2007] vs. 74.5% [2011], p < 0.01). Initiation rates also improved among 13–26 year-olds. Thus, the mean age at HPV1 receipt remained unchanged between 2007 and 2011 (16.0 ± 2.7 vs. 15.9 ± 4.0 years, p = 0.45). Spanish language was a positive predictor (AOR 1.62, 95% CI 1.05–2.48) of HPV vaccination initiation among 11–12 year-olds in 2011. The majority (70.8–76.4%) of unvaccinated subjects experienced missed vaccination opportunities. Of the subcohort, 36.9% underwent Chlamydia screening before HPV1 receipt (19.1% with ≥1 positive result). Of those with prior Papanicolaou screening (16.6%), 32.1% had ≥1 abnormal result.

Conclusions

These low-income, minority females frequently delayed initiation of HPV vaccination. Many had evidence of prior sexual experience and associated morbidity, placing them at risk of HPV-related complications. Promoting timely HPV vaccination and reducing missed vaccination opportunities are crucial.