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.     

‘Closing the gap’: Evaluating the success of non-mandatory strategies for influenza vaccination of Victorian healthcare workers

IntroductionWhile annual influenza vaccination of healthcare workers (HCWs) is recommended, uptake is often suboptimal. We sought to evaluate influenza vaccination uptake by HCWs in Victorian public healthcare facilities, where non-mandatory programs are used.MethodsAll participating facilities completed an annual survey (2014–2019) recording HCW influenza vaccination status. Uptake in high-risk departments (emergency and intensive care units) was evaluated for the 2019 season.ResultsThe proportion of vaccinated HCWs increased annually, from 72.2% (2014) to 87.7% (2019), with pre-set targets generally achieved. In 2019, 110,324 HCWs in 107 facilities were vaccinated (87.7%). Of those without documented vaccination, 7591 (6.0%) declined and 7906 (6.3%) had unknown status. Uptake was higher in high-risk departments (91.4%).ConclusionIncreasing annual influenza vaccination uptake by HCWs in Victorian public healthcare facilities has been achieved in the context of performance monitoring targets. Small proportions declined or had unknown status. Future policies should focus on these HCWs.     

Human papillomavirus vaccination: what is the best choice? A comparison of 16 strategies by means of a decisional model

SUMMARYSome European countries decided to include human papillomavirus (HPV) vaccines in national immunization schedules. In order to help decision makers choose the best vaccination policy for females, a decisional model has been developed. The study was performed from the National Health Service perspective. Several hypotheses of multi-cohort vaccination policies were compared. 'Potentially avoidable infections' were chosen as the outcome. The model envisioned a short-term scenario (2008-2011). The best policy was that of vaccinating 12-year-olds and, a year later, those aged 14-16 years; the most expensive strategy was that of vaccinating 12-year-old females and, after 1 year, vaccinating those aged 15, 18 and 25 years. The sensitivity analysis showed that coverage rate has a great effect on the cost of avoidable infections. The study offers stake-holders an important datum-point for the choice of the best HPV policy vaccination in the short term. Indeed, it could generate interesting savings for the National Health Service and a rapid HPV immunization of young girls.     

Two-dose strategies for human papillomavirus vaccination: How well do they need to protect?

Background

Two-dose human papillomavirus (HPV) vaccine schedules may provide short-term protection but their long-term population impact is unknown.

Methods

Two models of HPV transmission and associated cervical disease (squamous and glandular, neoplasia and cancer) were fitted to data from England and Canada on HPV epidemiology, sexual behaviour, cervical screening outcomes and cervical cancer incidence.

Results

Models suggest that at 40–80% coverage, if two-dose schedules protect vaccinees for 20 years, then the benefits of the third dose are small. If two doses protect for 10 years, then the third dose may prevent as many cancers as the first two. At 80% coverage, numbers needed to receive a third dose to prevent an additional cancer are 5900–110,000 (England), 3000–5100 (Canada) with 20 years two-dose protection, and 2000–5300 (England), 760–950 (Canada) with 10 years two-dose protection.

Conclusion

Results enable decision makers to quantify risks associated with two-dose schedules despite remaining uncertainties in vaccine duration and cross-protection.     

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.     

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.     

Parent perceptions of dentists’ role in HPV vaccination

IntroductionOffering HPV vaccine in settings beyond the traditional medical home holds promise for increasing the currently low levels of coverage. As adolescents frequently visit dentists, dental practices may be one such alternative vaccination setting. This study assessed parent attitudes about the roles dental providers could play in HPV prevention, including vaccine provision.MethodsIn September 2016, we conducted an online survey using a national sample (n = 1209) of U.S. parents of adolescent children aged 11–17. Adolescents’ mean age was 14; 53% were male and 62% were non-Hispanic white. We identified correlates of parents’ comfort with dentists as HPV vaccinators using multivariable logistic regression.ResultsOverall, 23% of parents reported that they would feel comfortable with their child receiving HPV vaccine from a dentist. In multivariable analyses, parents had greater odds of being comfortable if they had higher trust in their child’s primary care provider (OR = 1.27, 95% CI: 0.96–1.68) and lower odds if their child was female (OR = 0.65, 95% CI: 0.50–0.86). Convenience (20%) and oral health expertise (20%) were the most commonly cited benefits of dentists administering the vaccine. Wanting their child’s regular provider to administer and track vaccinations (61% and 58%, respectively), and lack of insurance coverage (30%) were the most commonly cited concerns. Parents expressed somewhat greater comfort with roles dentists might play in promoting HPV vaccination other than vaccine delivery, such as providing education.ConclusionsParents in this sample had low comfort with dentists as HPV vaccinators. Findings from this study highlight potential concerns to be addressed before dental practices consider offering HPV vaccination in the future. Further research should assess dentists’ perspectives and explore alternative roles for dental providers in HPV prevention efforts.     

Immunisation of chickens with live Salmonella vaccines – Role of booster vaccination

It is accepted that booster vaccinations of chickens with live Salmonella vaccines are essential part of vaccinations schemes to induce an effective adaptive immune response. As manufacturer of registered live Salmonella vaccines recommend different times of booster the question raises whether the duration between the first and second immunisation might influence the protective effect against Salmonella exposure. Chickens were immunised with a live Salmonella Enteritidis vaccine on day 1 of age followed by a booster vaccination at different intervals (day 28, 35 or 42 of age) to study the effects on the colonisation and invasion of the Salmonella vaccine strain, the humoral immune response and the efficacy against infection with Salmonella Enteritidis on day 56 of age. Immunisation of all groups resulted in a very effective adaptive immune response and a high degree of protection against severe Salmonella exposure, however, the time of booster had only an unverifiable influence on either the colonisation of the vaccine strain, the development of the humoral immune response or the colonisation of the Salmonella challenge strain. Therefore, the first oral immunisation of the chicks on day 1 of age seems to be of special importance and prerequisite for the development of the effective immune response. A booster immunisation should be carried out, however, the time of booster may vary between week 3 and week 7 of age of the chickens without adversely impact on the efficacy of the adaptive immune response or the protective effects.     

Decline of varicella vaccination in German surveillance regions after recommendation of separate first-dose vaccination for varicella and measles–mumps–rubella

Background

Germany introduced routine varicella (V) vaccination in 2004. Due to a slightly increased risk of febrile convulsions after first-dose application of combined measles–mumps–rubella–varicella (MMRV) vaccine separate first-dose vaccinations with MMR and monovalent V vaccine were recommended in September 2011.

Methods

We compared V and MMR vaccinations in paediatric practices from two surveillance regions (Munich and Würzburg) one year before and after the change in the recommendation.

Results

A total of 1405/326 monthly reports were provided by a monthly average of 79/14 practices participating in Munich/Würzburg. V first-dose vaccinations (monovalent V or MMRV vaccine) declined by 12% in Munich (from 10.1 to 8.9 vaccinations per month and practice; p < 0.005) and by 4% in Würzburg (from 9.9 to 9.5; p = 0.620), respectively. First-dose vaccinations for MMR (MMR or MMRV vaccine) did not change significantly in both regions.

Conclusion

Acceptance of V vaccination depends in part on the use of combination vaccine.     

Determinants of uptake of influenza vaccination among pregnant women – A systematic review

Background

Pregnant women have the highest priority for seasonal influenza vaccine. However, suboptimal coverage has been repeatedly noted in this population. To improve vaccine uptake, reviewing the determinants of vaccination is of increasing importance.

Methods

A detailed literature search was performed up to November 30, 2013 to retrieve articles related to uptake of influenza vaccination during pregnancy.

Results

Forty-five research papers were included in the review. Twenty-one studies assessed the coverage of seasonal influenza vaccination, 13 studies assessed coverage of A/H1N1 pandemic vaccination and 11 studies assessed both. Vaccination uptake ranged from 1.7% to 88.4% for seasonal influenza, and from 6.2% to 85.7% for A/H1N1 pandemic influenza. Many pregnant women were unaware that they were at high risk for influenza and its complications during pregnancy. They were also more likely to underestimate the threat of influenza to themselves and their fetus. Moreover, they had substantial concerns about the safety and efficacy of the influenza vaccine during pregnancy. Negative media reports contributed to the perception that influenza vaccination during pregnancy was risky and could result in adverse pregnancy outcomes. Although health care providers’ (HCPs) recommendations were consistently associated with vaccine uptake, most did not recommend the vaccine to their pregnant clients.

Conclusions

Influenza vaccination uptake among pregnant women is suboptimal and HCPs rarely recommend it. Positive vaccination recommendations from HCPs as well as direct access to the vaccine would likely substantially improve vaccination acceptance.     

Effect of media use on mothers’ vaccination of their children in sub-Saharan Africa

While several studies have examined the crucial role that parents’ vaccination behaviors play in reducing disease spread and severity among children, few have evaluated the connection between parents’ media use and their decision on whether or not to vaccinate their child, specifically in relation to the BCG (Bacillus Calmetter Guerin), DPT (Diptheria, Pertussis, Tetanus) polio, and measles vaccines. Media channels are a critical source of health information for parents, which is especially true in Sub-Saharan Africa, as there is often a dearth of local healthcare providers. The aim of this paper is to investigate the role that media use plays in a mothers’ choice to vaccinate their infant children in sub-Saharan Africa, specifically focusing on whether media use is associated with socioeconomic status (SES) and a mothers’ vaccination of their children. Cross-sectional data from the Demographic Health Surveys of 13 sub-Saharan countries (2004–2010) were pooled. A multivariate Poisson regression of 151,209 women was used to calculate adjusted relative ratios and 95% confidence intervals for the associations among SES, media use, and immunization. Education and wealth were found to be strongly and positively associated with vaccine-uptake behaviors. The effects of media use (radio and television) were found to be associated with the relationships between SES and vaccine uptake. However, it did not reduce the impact of SES on vaccination. These findings indicate that mass media may be an important tool for future efforts to reduce the health discrepancies between children from high- and low-socioeconomic backgrounds. Going forward, immunization strategies should include communication plans that will address and mitigate potential immunization disparities among parents of different SES backgrounds.     

Risk of Guillain-Barré syndrome after 2010–2011 influenza vaccination

Influenza vaccination has been implicated in Guillain Barré Syndrome (GBS) although the evidence for this link is controversial. A case–control study was conducted between October 2010 and May 2011 in seven Italian Regions to explore the relation between influenza vaccination and GBS. The study included 176 GBS incident cases aged ≥18 years from 86 neurological centers. Controls were selected among patients admitted for acute conditions to the Emergency Department of the same hospital as cases. Each control was matched to a case by sex, age, Region and admission date. Two different analyses were conducted: a matched case–control analysis and a self-controlled case series analysis (SCCS). Case–control analysis included 140 cases matched to 308 controls. The adjusted matched odds ratio (OR) for GBS occurrence within 6 weeks after influenza vaccination was 3.8 (95 % CI: 1.3, 10.5). A much stronger association with gastrointestinal infections (OR = 23.8; 95 % CI 7.3, 77.6) and influenza-like illness or upper respiratory tract infections (OR = 11.5; 95 % CI 5.6, 23.5) was highlighted. The SCCS analysis included all 176 GBS cases. Influenza vaccination was associated with GBS, with a relative risk of 2.1 (95 % CI 1.1, 3.9). According to these results the attributable risk in adults ranges from two to five GBS cases per 1,000,000 vaccinations.     

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.     

Impact of influenza vaccination on healthcare utilization – A systematic review

IntroductionAlthough a vaccine-preventable disease, influenza causes approximately 3–5 million cases of severe illness and about 290,000–650,000 deaths worldwide, which occur primarily among people 65 years and older. Nonetheless, prevention of influenza and its complications rely mainly on vaccination. We aimed to systematically evaluate influenza vaccine effectiveness at reducing healthcare utilization in older adults, defined as the reduction of outpatient visits, ILI and influenza hospitalizations, utilization of antibiotics and cardiovascular events by vaccination status during the influenza season.MethodsWe searched MEDLINE, EMBASE, CINAHL, Cochrane Library and considered any seasonal influenza vaccine, excluding the pandemic (2009–10 season) vaccine. Reviewers independently assessed data extraction and quality assessment.ResultsOf the 8308 citations retrieved, 22 studies were included in the systematic review. Overall, two studies (9%) were deemed at moderate risk of bias, thirteen (59%) at serious risk of bias and seven (32%) at critical risk of bias. For outpatient visits, we found modest evidence of protection by the influenza vaccine. For all-cause hospitalization outcomes, we found a wide range of results, mostly deemed at serious risk of bias. The included studies suggested that the vaccine may protect older adults against influenza hospitalizations and cardiovascular events. No article meeting our inclusion criteria explored the use of antibiotics and ILI hospitalizations. The high heterogeneity between studies hindered the aggregation of data into a meta-analysis.ConclusionThe variability between studies prevented us from drawing a clear conclusion on the effectiveness of the influenza vaccine on healthcare utilization in older adults. Overall, the data suggests that the vaccine may result in a reduction of healthcare utilization in the older population. Further studies of higher quality are necessary.     

Costs implications of pneumococcal vaccination of adults aged 30–60 with a recent diagnosis of diabetes

ObjectiveThe 23-valent pneumococcal polysaccharide vaccine is routinely recommended for adults with diabetes, but little is known about adherence to this recommendation and how vaccination of these adults affects costs related to pneumococcal disease.Research design and methodsWe used data from a commercial insurance claims dataset to examine a cohort of non-elderly adults with a new diagnosis of diabetes and adults with no diagnosis of diabetes from 2005 to 2014. We examined rates of pneumococcal polysaccharide vaccination and the relationship between vaccination and pneumococcal disease costs, comparing results for persons with a diagnosis of diabetes and those with no diagnosis of diabetes.ResultsOverall rates of pneumococcal polysaccharide vaccination among adults 30–60 years old were <1%/year. Rates of pneumococcal polysaccharide vaccination were higher for adults with diabetes. Pneumococcal polysaccharide vaccination rates more than doubled from 2.9% per year in 2005 to 6.0% per year in 2014 for adults vaccinated during the same year as their diabetes diagnosis. Using a two-part differences-in-differences model on a propensity-score matched dataset, pneumococcal polysaccharide vaccination may reduce average annual per-person pneumococcal disease costs by $90.54 [95% CI: $183.59, -$2.49, (p = 0.056)] in persons with diabetes from two years before to two years after vaccination.ConclusionsNon-elderly adults with diabetes have low but rising rates of pneumococcal polysaccharide vaccination. Pneumococcal polysaccharide vaccination has a modest impact reducing overall costs of pneumococcal disease in this population.     

A cost-effectiveness analysis of South Africa’s seasonal influenza vaccination programme

BackgroundSeasonal influenza imposes a significant health and economic burden in South Africa, particularly in populations vulnerable to severe consequences of influenza. This study assesses the cost-effectiveness of South Africa’s seasonal influenza vaccination strategy, which involves vaccinating vulnerable populations with trivalent inactivated influenza vaccine (TIV) during routine facility visits. Vulnerable populations included in our analysis are persons aged ≥ 65 years; pregnant women; persons living with HIV/AIDS (PLWHA), persons of any age with underlying medical conditions (UMC) and children aged 6–59 months.MethodWe employed the World Health Organisation’s (WHO) Cost Effectiveness Tool for Seasonal Influenza Vaccination (CETSIV), a decision tree model, to evaluate the 2018 seasonal influenza vaccination campaign from a public healthcare provider and societal perspective. CETSIV was populated with existing country-specific demographic, epidemiologic and coverage data to estimate incremental cost-effectiveness ratios (ICERs) by comparing costs and benefits of the influenza vaccination programme to no vaccination.ResultsThe highest number of clinical events (influenza cases, outpatient visits, hospitalisation and deaths) were averted in PLWHA and persons with other UMCs. Using a cost-effectiveness threshold of US$ 3 400 per quality-adjusted life year (QALY), our findings suggest that the vaccination programme is cost-effective for all vulnerable populations except for children aged 6–59 months. ICERs ranged from ~US$ 1 750 /QALY in PLWHA to ~US$ 7 500/QALY in children. In probabilistic sensitivity analyses, the vaccination programme was cost-effective in pregnant women, PLWHA, persons with UMCs and persons aged ≥65 years in >80% of simulations. These findings were robust to changes in many model inputs but were most sensitive to uncertainty in estimates of influenza-associated illness burden.ConclusionSouth Africa's seasonal influenza vaccination strategy of opportunistically targeting vulnerable populations during routine visits is cost-effective. A budget impact analysis will be useful for supporting future expansions of the programme.