National and state-specific estimates of place of influenza vaccination among adult populations – United States, 2011–12 influenza season

Background

Annual influenza vaccination has been recommended for all persons ≥6 months since the 2010–11 season. New partnerships between public health agencies and medical and nonmedical vaccination providers have increased the number of vaccination providers and locations where vaccination services are delivered.

Methods

Data from the 2011–12 Behavioral Risk Factor Surveillance System (BRFSS) were analyzed. Point estimates of place of vaccination and 95% confidence intervals were calculated. Multivariable logistic regression and predictive marginal modeling were conducted to identify factors associated with vaccination settings.

Results

Among adults vaccinated during the 2011–12 influenza season, a doctor's office was the most common place (38.4%) for receipt of influenza vaccination, with stores (e.g., supermarkets or drug stores) (20.1%) the next common, and workplaces (17.6%) the third common. Overall, reported vaccination in nonmedical settings by state ranged from 32.2% in California to 60.4% in Nevada, with a median of 45.8%. Characteristics significantly associated with an increased likelihood of receipt of vaccination in nonmedical settings were higher education, not having certain identified high-risk conditions, not having had a routine checkup in the previous 12 months, and not having a primary doctor for health care. Being a member of a racial/ethnic minority group, unemployed or not in the work force were significantly associated with a decreased likelihood of receipt of vaccination in nonmedical settings.

Conclusion

Doctor's offices were the most common medical setting for adult influenza vaccination; workplaces and stores were important nonmedical settings. Increasing access to vaccination services in medical and nonmedical settings should be considered as important strategies for improving vaccination coverage. These results also can help guide development of strategies for achieving Healthy People 2020 objectives for influenza vaccination of adult populations.     

Age-specific differences in influenza A epidemic curves: do children drive the spread of influenza epidemics?

There is accumulating evidence suggesting that children may drive the spread of influenza epidemics. The objective of this study was to quantify the lead time by age using laboratory-confirmed cases of influenza A for the 1995/1996-2005/2006 seasons from Canadian communities and laboratory-confirmed hospital admissions for the H1N1/2009 pandemic strain. With alignment of the epidemic curves locally before aggregation of cases, slight age-specific differences in the timing of infection became apparent. For seasonal influenza, both the 10-19- and 20-29-year age groups peaked 1 week earlier than other age groups, while during the fall wave of the 2009 pandemic, infections peaked earlier among only the 10-19-year age group. In the H3N2 seasons, infections occurred an average of 3.9 (95% confidence interval: 1.7, 6.1) days earlier in the 20-29-year age group than for youth aged 10-19 years, while during the fall pandemic wave, the 10-19-year age group had a statistically significant lead of 3 days compared with both younger children aged 4-9 years and adults aged 20-29 years (P < 0.0001). This analysis casts doubt on the hypothesis that younger school-age children actually lead influenza epidemic waves.     

The faces of influenza vaccine recommendation: A Literature review of the determinants and barriers to health providers’ recommendation of influenza vaccine in pregnancy

IntroductionWHO recommends influenza vaccination for pregnant women and health providers (HPs), yet global uptake for both is persistently low. Research suggests that HPs greatly influence uptake of influenza vaccine in pregnant women. Our review studies HPs’ recommendation of influenza vaccine to pregnant women, determinants and barriers to recommendation, and the role that HPs may play in global influenza vaccine coverage.MethodsWe undertook a comprehensive global review of literature relating to HPs’ recommendation of seasonal influenza vaccines to pregnant women and the determinants and barriers to recommendation and how this may vary by country and context. We evaluated data from each study including frequency of HP recommendation, vaccine coverage, determinants and barriers to recommendation, and the odds of recommending. We tracked the frequency of determinants and barriers to recommendation in heat maps and organized data by world regions and income classifications.ResultsFrom 32 studies in 15 countries, we identified 68 determinants or barriers to HPs’ recommendation. Recommendation rates were highest (77%) in the Americas and lowest in South East Asia (18%). A HP’s own influenza vaccine status was a main determinant of recommendation in multiple country contexts and from different provider types. Financial barriers to recommendation were present in higher-income countries and policy-related barriers were highlighted in lower-income countries. HP perceptions of safety, efficacy, and the utility of vaccine were the most frequently cited barriers, relevant in almost every context.ConclusionsHP recommendation is important to influenza vaccine implementation in pregnant women. A HP’s own status is an important recommendation determinant in multiple contexts. Vaccine program implementation plans should consider the impact of HPs' knowledge, awareness and vaccine confidence on their own uptake and recommendation practices, as well as on the uptake among pregnant women. Addressing safety and efficacy concerns is relevant in all contexts for HPs and pregnant women.     

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.     

Three-season effectiveness of inactivated influenza vaccine in preventing influenza illness and hospitalization in children in Japan, 2013–2016

ObjectivesWe assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children 6 months to 15 years of age in 2015/16 season. In addition, based on the data obtained during the three seasons from 2013 to 2016, we estimated the three-season VE in preventing influenza illness and hospitalization.MethodsOur study was conducted according to a test-negative case-control design (TNCC) and as a case-control study based on influenza rapid diagnostic test results.ResultsDuring 2015/16 season, the quadrivalent IIV was first used in Japan. The adjusted VE in preventing influenza illness was 49% (95% confidence interval [CI]: 42–55%) against any type of influenza, 57% (95% CI: 50–63%) against influenza A and 34% (95% CI: 23–44%) against influenza B. The 3-season adjusted VE was 45% (95% CI: 41–49%) against influenza virus infection overall (N = 12,888), 51% (95% CI: 47–55%) against influenza A (N = 10,410), and 32% (95% CI: 24–38%) against influenza B (N = 9232). An analysis by age groups showed low or no significant VE in infants or adolescents. By contrast, VE was highest in the young group (1–5 years old) and declined with age thereafter. The 3-season adjusted VE in preventing hospitalization as determined in a case-control study was 52% (95% CI: 42–60%) for influenza A and 28% (95% CI: 4–46%) for influenza B, and by TNCC design, it was 54% (95% CI: 41–65%) for influenza A and 34% (95% CI: 6–54%) for influenza B.ConclusionWe demonstrated not only VE in preventing illness, but also VE in preventing hospitalization based on much larger numbers of children than previous studies.     

Priority allocation of pandemic influenza vaccines in Australia – Recommendations of 3 community juries

BackgroundPandemic planning has historically been oriented to respond to an influenza virus, with vaccination strategy being a key focus. As the current COVID-19 pandemic plays out, the Australian government is closely monitoring progress towards development of SARS-CoV2 vaccines as a definitive intervention. However, as in any pandemic, initial supply will likely be exceeded by demand due to limited manufacturing output.MethodsWe convened community juries in three Australian locations in 2019 to assess public acceptability and perceived legitimacy of influenza pandemic vaccination distribution strategies. Preparatory work included literature reviews on pandemic vaccine allocation strategies and on vaccine allocation ethics, and simulation modelling studies. We assumed vaccine would be provided to predefined priority groups. Jurors were then asked to recommend one of two strategies for distributing remaining early doses of vaccine: directly vaccinate people at higher risk of adverse outcomes from influenza; or indirectly protect the general population by vaccinating primary school students, who are most likely to spread infection.ResultsThirty-four participants of diverse backgrounds and ages were recruited through random digit dialling and topic-blinded social media advertising. Juries heard evidence and arguments supporting different vaccine distribution strategies, and questioned expert presenters. All three community juries supported prioritising school children for influenza vaccination (aiming for indirect protection), one by 10–2 majority and two by consensus. Justifications included that indirect protection benefits more people and is likely to be more publicly acceptable.ConclusionsIn the context of an influenza pandemic, informed citizens were not opposed to prioritising groups at higher risks of adverse outcomes, but if resources and epidemiological conditions allow, achieving population benefits should be a strategic priority. These insights may inform future SARS-CoV-2 vaccination strategies.     

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.     

On the bias of estimates of influenza vaccine effectiveness from test–negative studies

Estimates of the effectiveness of influenza vaccines are commonly obtained from a test-negative design (TND) study, where cases and controls are patients seeking care for an acute respiratory illness who test positive and negative, respectively, for influenza infection. Vaccine effectiveness (VE) estimates from TND studies are usually interpreted as vaccine effectiveness against medically-attended influenza (MAI). However, it is also important to estimate VE against any influenza illness (symptomatic influenza (SI)) as individuals with SI are still a public health burden even if they do not seek medical care. We present a numerical method to evaluate the bias of TND-based estimates of influenza VE with respect to MAI and SI. We consider two sources of bias: (a) confounding bias due to a (possibly unobserved) covariate that is associated with both vaccination and the probability of the outcome of interest and (b) bias resulting from the effect of vaccination on the probability of seeking care. Our results indicate that (a) VE estimates may suffer from substantial confounding bias when a confounder has a different effect on the probabilities of influenza and non-influenza ARI, and (b) when vaccination reduces the probability of seeking care against influenza ARI, then estimates of VE against MAI may be unbiased while estimates of VE against SI may be have a substantial positive bias.     

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.     

Monitoring of influenza viruses in Western Siberia in 2008–2012

Western Siberia is of great importance in ecology and epidemiology of influenza. This territory is nesting area for great amount of bird species. Territorial relations of Western Siberian birds that are established during seasonal migration are extremely wide since this region is an intersection point of bird migration flows wintering in different regions of the world: Europe, Africa, Middle East, Central Asia, Hindustan, and South East Asia. Reassortant influenza viruses that can cause outbreak among population may emerge in Western Siberia with high probability. Thus, it is extremely important to carry out widespread study of circulated viruses, their molecular biological properties, phylogenetic links in this region, as well as herd immunity to influenza virus serotypes with epidemic potential.     

Survey of distribution of seasonal influenza vaccine doses in 201 countries (2004–2015): The 2003 World Health Assembly resolution on seasonal influenza vaccination coverage and the 2009 influenza pandemic have had very little impact on improving influenza control and pandemic preparedness

There is no global monitoring system for influenza vaccination coverage, making it difficult to assess progress towards the 2003 World Health Assembly (WHA) vaccination coverage target. In 2008, the IFPMA Influenza Vaccine Supply International Task Force (IVS) developed a survey method to assess the global distribution of influenza vaccine doses as a proxy for vaccination coverage rates. The latest dose distribution data for 2014 and 2015 was used to update previous analyses. Data were confidentially collected and aggregated by the IFPMA Secretariat, and combined with previous IFPMA IVS survey data (2004–2013). Data were available from 201 countries over the 2004–2015 period. A “hurdle” rate was defined as the number of doses required to reach 15.9% of the population in 2008. Overall, the number of distributed doses progressively increased between 2004 and 2011, driven by a 150% increase in AMRO, then plateaued. One percent fewer doses were distributed in 2015 than in 2011. Twenty–three countries were above the hurdle rate in 2015, compared to 15 in 2004, but distribution was highly uneven in and across all WHO regions. Three WHO regions (AMRO, EURO and WPRO) accounted for about 95% of doses distributed. But in EURO and WPRO, distribution rates in 2015 were only marginally higher than in 2004, and in EURO there was an overall downward trend in dose distribution. The vast majority of countries cannot meet the 2003 WHA coverage targets and are inadequately prepared for a global influenza pandemic. With only 5% of influenza vaccine doses being distributed to 50% of the world’s population, there is urgency to redress the gross inequities in disease prevention and in pandemic preparedness. The 2003 WHA resolution must be reviewed and revised and a call issued for the renewed commitment of Member States to influenza vaccination coverage targets.     

Effectiveness of inactivated influenza and COVID-19 vaccines in hospitalized children in 2022/23 season in Japan – The first season of co-circulation of influenza and COVID-19

We have analyzed the inactivated vaccine effectiveness (VE) for preventing influenza hospitalization by test-negative design in the 2022/23 season. This is the first season of co-circulation of influenza and COVID-19, and a unique period because all inpatients received COVID-19 screening. Among 536 children hospitalized with fever, none were positive for both influenza and SARS-CoV-2. The adjusted VE for preventing influenza A for all children, the 6–12-year-old group, and those with underlying diseases was 34 % (95 ％CI, −16 %–61 %, n = 474), 76 % (95 ％ CI, 21 %–92 %, n = 81), and 92 % (95 ％ CI, 30 %–99 %, n = 86), respectively. Only 1 out of 35 hospitalized cases with COVID-19, and 42 out of 429 controls, had been immunized with COVID-19 vaccine. This is the first report showing influenza VE by age group in children in this limited season. We still recommend the inactivated influenza vaccine for children based on the significant VE in subgroup analysis.     

A real-world study evaluating the relative vaccine effectiveness of a cell-based quadrivalent influenza vaccine compared to egg-based quadrivalent influenza vaccine in the US during the 2017–18 influenza season

BackgroundCell-based influenza vaccine manufacturing reduces egg adaptations that can decrease vaccine effectiveness. We evaluated the relative vaccine effectiveness (rVE) of cell-based quadrivalent influenza vaccine (QIVc) compared to standard-dose egg-based quadrivalent influenza vaccines (QIVe-SD) against influenza-related and serious respiratory events among subjects 4–64 years of age during the 2017–18 influenza season.MethodsA retrospective cohort analysis was conducted using administrative claims data in the US (IQVIA PharMetrics Plus® database). Subjects vaccinated with QIVc or QIVe-SD from 8/2017–1/2018 were identified (date of vaccination termed the index date). Influenza-related hospitalizations/ER visits, all-cause hospitalizations and serious respiratory hospitalizations/ER visits were assessed post-vaccination. Inverse probability of treatment weighting (IPTW) and Poisson regression were used to evaluate the adjusted rVE of QIVc compared to QIVe-SD. In a subgroup analysis, rVE was assessed for several subgroups of interest (4–17, 18–64 and 50–64 years, and subjects with ≥1 high-risk condition). In a secondary economic analysis, annualized all-cause costs over the follow-up were compared using propensity score matching (PSM) and generalized estimating equation (GEE) models.ResultsThe study sample comprised 555,538 QIVc recipients and 2,528,524 QIVe-SD recipients. Prior to adjustment, QIVc subjects were older and had higher total costs in the 6-months pre-index. Following IPTW-adjustment and Poisson regression, QIVc was more effective in reducing influenza-related hospitalizations/ER visits, all-cause hospitalizations, and hospitalizations/ER visits related to asthma/COPD/bronchial events and other respiratory events compared to QIVe-SD. Similar trends were generally observed in the subgroup analysis. Following PSM adjustment and GEE regression, QIVe-SD was associated with significantly higher annualized all-cause total costs compared to QIVc, driven by higher costs for outpatient medical services and inpatient hospitalizations.ConclusionsAfter adjustment for confounders and selection bias, QIVc reduced influenza-related hospitalizations/ER visits, all-cause hospitalizations, and serious respiratory hospitalizations/ER visits compared to QIVe-SD. QIVc was associated with significantly lower all-cause total costs.     

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.     

Development of a live-attenuated influenza B ΔNS1 intranasal vaccine candidate

We discovered a unique, single amino acid mutation in the influenza B M1 protein promoting viral growth of NS1 truncation mutants in Vero cells. Due to this mutation, we were able to generate an influenza B virus lacking the complete NS1 open reading frame (ΔNS1-B virus) by reverse genetics, which was growing to titers of 8 log₁₀ TCID₅₀/ml in a Vero cell culture-based micro-carrier fermenter. The ΔNS1-B vaccine candidate was attenuated in IFN-competent hosts such as human alveolar epithelial cells (A549) similar to influenza A ΔNS1 viruses. In ferrets, the ΔNS1-B virus was replication-deficient and did not provoke any clinical symptoms. Importantly, a single intranasal immunization of ferrets at a dose as low as 6 log₁₀ TCID₅₀/animal induced a significant HAI response and provided protection against challenge with wild-type influenza B virus. So far, the lack of a ΔNS1-B virus component growing to high titers in cell culture has been limiting the possibility to formulate a trivalent vaccine based on deletion of the NS1 gene. Our study closes this gap and paves the way for the clinical evaluation of a seasonal, trivalent, live replication-deficient ΔNS1 intranasal influenza vaccine.